Archived DocumentÑ Prostate Cancer For Reference Only

Report onReport on

CLINICAL PRACTICE GUIDELINES

The American Urological AssociationProstate Cancer Clinical Guidelines Panel

The Management ofClinically LocalizedProstate Cancer

The Management ofClinically LocalizedProstate CancerArchived Document—

For Reference Only

Richard G. Middleton, MD(Panel Co-Chairman)Department of UrologyThe University of UtahSalt Lake City, Utah

Ian M. Thompson, MD(Panel Co-Chairman)Urology ServiceBrooke Army Medical CenterSan Antonio, Texas

Mark S. Austenfeld, MD(Panel Facilitator)Department of UrologyThe University of Kansas MedicalCenter

Kansas City, Kansas

William H. Cooner, MDDepartment of UrologyEmory UniversityAtlanta, Georgia

Roy J. Correa, Jr., MDDepartment of UrologyThe Virginia Mason ClinicSeattle, Washington

Robert P. Gibbons, MDDepartment of UrologyThe Virginia Mason ClinicSeattle, Washington

Harry C. Miller, Jr., MDDepartment of UrologyThe George Washington UniversityWashington, D.C.

Joseph E. Oesterling, MDDivision of Urology and the MichiganProstate Institute

The University of MichiganAnn Arbor, Michigan

Martin I. Resnick, MDDepartment of UrologyCase Western Reserve UniversityCleveland, Ohio

Stephen R. Smalley, MDTherapeutic Radiologists, Inc.Kansas City, Missouri

John H. Wasson, MDProstate Patient Outcomes ResearchTeam

Dartmouth Medical SchoolHanover, New Hampshire

Claus G. Roehrborn, MD(Facilitator Coordinator)Division of UrologyThe University of Texas SouthwesternMedical Center

Dallas, Texas

Hanan S. Bell, PhD(Consultant in Methodology)Seattle, Washington

Brent Blumenstein, PhD(Consultant in Biostatistics)Fred Hutchinson Cancer CenterSeattle, Washington

Scott Optenberg, Dr. PH(Consultant for Health CareEconomics)

Clinical Investigation ActivityU.S. Army Health Services CommandSan Antonio, Texas

Patrick M. Florer(Database Design and Coordination)Dallas, Texas

Curtis Colby(Editor)Washington, D.C.

Prostate Cancer Clinical Guidelines Panel Members and Consultants

Dedication

This report is dedicated to the memory of William H. Cooner, MD, who lentinvaluable support, time and encouragement to the efforts of the panel.

The Prostate Cancer Clinical Guidelines Panel consists of board-certified urologists and other ex-perts in prostate cancer management. This Report on the Management of Clinically Localized ProstateCancerwas extensively reviewed by nearly 40 urologists throughout the country in early 1995. Thepanel finalized its recommendations for the AUA’s Practice Parameters, Guidelines and StandardsCommittee, chaired by Winston K. Mebust, MD, in June 1995. The AUA Board of Directors approvedthese practice guidelines in July 1995.

The Summary Report also underwent independent scrutiny by the Editorial Board of the Journalof Urology, was accepted for publication in August 1995 and appeared in its December issue. APatient’s Guideand a Technical Supplementhave also been developed; both are available from theAUA.

The American Urological Association expresses its gratitude for the dedication and leadershipdemonstrated by the members of the Prostate Cancer Clinical Guidelines Panel in producing thisguideline.

Members Consultants

ISBN 0-9649702-0-1

Archived Document— For Reference Only

Page iCopyright © 1995 American Urological Association, Inc.

Prostate cancer is the most common nondermatologic malignancy and thesecond most common cause of cancer death among men in the United States.In 1995, an estimated 244,000 new cases were anticipated, and prostate cancerdeaths were estimated at 40,400 (Wingo, Tong and Bolden, 1995). For a whitemale born in 1988-1990, the lifetime risk of developing clinically apparentprostate cancer is 13.34 percent. For an African-American male, the risk is11.27 percent (Miller, Hayes, Potosky, et al., 1993). Lifetime risks of deathfrom prostate cancer in these two groups are 3.18 percent and 3.96 percent, re-spectively. Because of an aging U.S. population, the number of men recog-nized to have prostate cancer will rise dramatically over the next 20 years.During the next 10 years, it is estimated that there will be a 90-percent in-crease in prostate cancer detection and a 37-percent increase in prostate cancerdeaths (Carter and Coffey, 1990).

Enhanced early detection techniques using digital rectal examination (DRE)and prostate specific antigen (PSA), as well as more public awareness of pros-tate cancer, have greatly increased rates of diagnosis. One result has been ashift toward more tumors detected at lower stages. In 1982, an American Col-lege of Surgeons survey found the following percentages, by clinical stage, ofnewly diagnosed prostate tumors: stage T1 (A), 25.9 percent; stage T2 (B),28.9 percent; stages T3-T4 (C), 14.9 percent; stage M1 (D2), 24.9 percent(Murphy, Natarajan, Pontes, et al., 1982). A 1990 survey found that more new-ly diagnosed tumors were organ confined: stage T1 (A), 29.3 percent; stage T2(B), 37.7 percent; stages T3-T4 (C), 12.5 percent; and stage M1 (D2), 20.6percent (Mettlin, Jones and Murphy, 1993). At a number of institutions wherePSA is an integral part of early diagnosis, as many as 99 percent of prostatecancers diagnosed during serial PSA-based screening have been clinically or-gan confined, and 75 percent pathologically organ confined (Catalona, Smith,Ratliff, et al., 1993).

With this growth in numbers of locally confined tumors found through earlydetection efforts has come greater scrutiny of the methods of treatment. A 1988National Institutes of Health (NIH) consensus conference, employing an im-plicit approach to the development of conclusions, compared the efficacy ofsurgical therapy and radiotherapy. It was not possible, based upon available da-ta, to determine the optimal treatment for localized disease (NIH ConsensusDevelopment Panel, National Cancer Institute’s Monograph No. 7, 1988).

Since that time, the publication of a number of series on the management ofclinically localized prostate cancer by surveillance (no treatment) has increasedthe uncertainty as to the optimal treatment for this stage of disease. For low-grade tumors, these series have generally reported cancer-specific survivalswith management by surveillance that do not differ significantly from cancer-

Introduction


Page ii Copyright © 1995 American Urological Association, Inc.

specific survivals following treatment by surgery or radiotherapy for periods upto 10 years (Johansson, Adami, Andersson, et al., 1992; Whitmore, Warner andThompson, 1991). Pooled analyses and decision analyses employing data fromsurveillance series have further clouded the question of optimal treatment forlocalized disease (Chodak, Thisted, Gerber, et al., 1994; Fleming, Wasson,Albertsen, et al., 1993).

Recognizing the need for a systematic analysis of the literature regardingthe available methods of treatment for localized prostate cancer, and in the ab-sence of a randomized, prospective comparison of these methods, theAmerican Urological Association (AUA) in 1989 convened the Prostate CancerClinical Guidelines Panel to conduct a comprehensive survey and analysis ofpublished data. This document,Report on the Management of Clinically Local-ized Prostate Cancer,is the product of that effort.

This report, as its title indicates, focuses on the treatment of tumors con-fined within the prostate, specifically clinical stage T2 (B) tumors. (“Stage” inthis document means “clinical stage” unless “pathological stage” is specified.)Inevitably discussed in this report are stages other than T2, questions regardingstaging methods and various issues related to the diagnosis as well as treatmentof prostate cancer in general. However, the panel’s analysis and recommenda-tions are intended to apply only to treatment of clinically localized prostatecancer.

The report summarizes the methodology employed by the panel, displaysthe outcomes evidence extracted from the prostate cancer treatment literatureand recommends practice policies for the management of clinical stage T2 (B)prostate cancer insofar as the evidence permits. The report also includes analy-sis of the limitations in the treatment literature regarding outcomes evidenceand makes recommendations for further research.

A summary of this report has been published in the Journal of UrologyDecember 1995: Vol. 154, pgs. 2144 – 2148. A 12-page Patient’s Guidein-cluding illustrations of the progressions of prostate cancer is available to assistthe physician in discussing treatment options with the patient. Also available isa Technical Supplementproviding more detailed displays of the data analysis.


Page iiiCopyright © 1995 American Urological Association, Inc.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .iExecutive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1

Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1Treatment alternatives and treatment outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . .2Treatment recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3Literature limitations and recommendations for research . . . . . . . . . . . . . . . . . . . . .6

Chapter 1: Methodology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Methods and definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8Literature search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9Data extraction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9Data inadequacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9Data display for survival and disease progression . . . . . . . . . . . . . . . . . . . . . . . . . .10Treatment complications data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10Literature citations and panel opinions in discussion sections . . . . . . . . . . . . . . . . .10

Chapter 2: Prostate cancer and its management . . . . . . . . . . . . . . . . . . . . . . . . . . .12Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12Natural history and grade classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12Staging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13Treatment alternatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15

Chapter 3: Outcomes of treatments for localized prostate cancer . . . . . . . . . . . . .21Types of outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .21Variability of outcomes data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22Summary outcomes tables and graphs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .22Analysis of summary outcomes tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .32Treatment complications summary outcomes table and graphs . . . . . . . . . . . . . . . .35Analysis of treatment complications summary outcomes table . . . . . . . . . . . . . . . . .36

Chapter 4: Treatment recommendations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37The standard patient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37Recommendations: Standards . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .37Recommendations: Treatment options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .38Advantages and disadvantages of treatment options . . . . . . . . . . . . . . . . . . . . . . . . .38

Chapter 5: Literature limitations and recommendations for research . . . . . . . . . .42Limitations in the prostate cancer treatment literature . . . . . . . . . . . . . . . . . . . . . . .42Recommendations for future research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .43

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .46Appendix A: Data presentation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .A-1Appendix B: Data abstraction form . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .B-1Appendix C: U.S. life expectancy table . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .C-1Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .I-1


Production and layout by

Lisa EmmonsTracy Kiely

Betty Roberts

Copyright © 1995American Urological Association, Inc.


Page 1 Executive SummaryCopyright © 1995, American Urological Association, Inc.

In developing recommendations for the manage-ment of clinically localized prostate cancer, theAUA Prostate Cancer Clinical Guidelines Panel ex-tensively reviewed the prostate cancer treatment lit-erature from 1966 to December 1993 and extractedall relevant data to estimate as accurately as possi-ble desirable and undesirable outcomes of the alter-native treatment modalities. The panel followed anexplicit approach to guideline development (Eddy,1992). This approach emphasizes use of scientificevidence in estimating outcomes of interventions.When panel opinion is necessary, the explicit ap-proach calls for explaining why and discussing thefactors considered. For a full description of themethodology, see Chapter 1.

Of the malignant conditions that arise primarilywithin the prostate gland, by far the most frequentlyoccurring type is adenocarcinoma. Because of therarity of other primary neoplasms within the gland,the terms “prostate cancer” and “carcinoma of theprostate” are generally understood to be synony-mous with “adenocarcinoma.”

Adenocarcinoma of the prostate is the most com-monly diagnosed visceral neoplasm in men. The es-timated 244,000 new cases diagnosed in 1995 rep-resent 36 percent of cancers in men, compared with14 percent for lung cancer and 10.4 percent for col-orectal cancer, the next two most frequently diag-nosed cancers (Wingo, Tong and Bolden, 1995).The 40,400 deaths from prostate cancer anticipatedin 1995 represent 14 percent of all cancer deaths inmen, placing prostate cancer second only to lungcancer mortality (33 percent) and ahead of colorec-tal cancer mortality (9.4 percent).

Natural historyProstate cancer has a wide spectrum of growth

rates. Many tumors pursue a relatively indolent

course over many years. Others advance rapidly bylocal extension and/or metastasis. Evaluation of theeffect of active intervention must take into accountthe course the disease would follow if allowed toproceed without interference. Active treatment of aprostatic cancer destined never to present a clinicalproblem would not be expected to improve patientoutcomes over treatment by surveillance alone.Prostate cancer aggressiveness, however, does tendto increase with time (Adolfsson and Tribukait,1990). Given sufficient time, small localized tumorscan be expected to become large, multifocal, nonlo-calized tumors (Whitmore, Warner and Thompson,1991), with decreasing likelihood of cure. “Cure” isdefined in this report as lifetime freedom from dis-ease.

Thus, patient longevity becomes a major consid-eration, especially since techniques to distinguishrapidly growing from slow-growing tumors are stillevolving. Treatment of prostate cancer depends to asignificant degree upon the patient’s age, functionallevel and medical status. Factors such as tumor vol-ume (stage) and grade, along with evaluation of nu-clear chromatin content and nuclear roundness, al-low some prediction of a tumor’s biologic potential.However, at present, such factors are not all fullyapplicable to individual patients because of themany exceptions to these predictive indices.

StagingAccurate determination of tumor stage is impor-

tant, in that therapy is highly dependent upon theknowledge of whether the tumor is localized to thegland. Several staging systems for prostate cancerhave been described. The two most often used arethe Jewett-Whitmore (ABCD) system and theAmerican Joint Committee (TNM) system. Theyare shown in Table 1 on page 13. A new clinicalstage has been designated primarily for PSA-detect-ed prostate cancers. In the TNM staging system,these tumors are categorized as stage T1c and in theJewett-Whitmore staging system as stage B0.

Clinical staging has improved in recent years,but considerable inaccuracy remains. The result canbe understaging or, to a lesser extent, overstaging ascompared with surgical or pathologic staging. This

Background

Methodology

Executive summary:Report on the management of clinically localized prostate cancer


Page 2 Executive Summary Copyright © 1995, American Urological Association, Inc.

has confounded accurate evaluation of treatmentmodalities based solely upon clinical staging.

Methods available for the staging of clinicallylocalized prostate cancer include digital rectal ex-amination (DRE), serum prostate specific antigen(PSA), serum acid phosphatase, transrectal ultra-sonography (TRUS), computerized tomography(CT) scan and magnetic resonance imaging (MRI).For determination of distant metastases, stagingmethods include CT scan, MRI and radioisotopicbone scan. In the panel’s opinion and based ongrowing evidence from recent studies, many of themethods available do not necessarily provide usefulinformation and may not be required for patientswith clinically localized prostate cancer.

Regarding clinical staging, several conclusionscan be drawn from the medical literature that affectclinical practice:

(1) CT scan and MRI may not be required in thestaging evaluation of patients with clinically local-ized prostate cancer. These tests can often detectgross extraprostatic disease, but that degree ofspread can usually be predicted by the serum PSAconcentration, DRE or TRUS at time of biopsy.Capsular perforation, seminal vesicle invasion andpelvic lymph node involvement most often are mi-croscopic phenomena and cannot be diagnosed byeither CT scan or MRI.

(2) Evidence is mounting that the majority ofpatients who are candidates for a radical prostatec-tomy or radiotherapy have a very low risk of havingpositive pelvic lymph nodes. When the serum PSAconcentration, tumor grade and local clinical stageused together are below certain levels, a pelviclymph node dissection may not be necessary be-cause, as noted on page 15, the probability of posi-tive lymph nodes is extremely low.

(3) From the results of two large clinical studies(Chybowski, Larson-Keller, Bergstralh, et al., 1991;Oesterling, Martin, Bergstralh, et al., 1993), it ap-pears that a staging radionuclide bone scan may notbe necessary for patients with newly diagnosed, un-treated prostate cancer who have no skeletal symp-toms and a serum PSA of 10 ng/ml or less.

The following treatment alternatives in currentuse for managing localized prostate cancer, eitheralone or in various combinations, were analyzed bythe AUA Prostate Cancer Clinical Guidelines Panel:

radical prostatectomy, external beam radiotherapy,brachytherapy (interstitial radiotherapy) and sur-veillance (also known as expectant management,watchful waiting or observation). Treatment meth-ods considered investigational are thermotherapy,cryotherapy, androgen deprivation and chemothera-py. The panel categorized a treatment method as in-vestigational if the number of patients treated hasbeen inadequate for evaluation and/or if follow-uphas been inadequate to provide sufficiently preciseoutcome estimates.

Treatment outcomesFor assessing the benefits and harms of treatment

interventions for stage T2 (B) prostate malignancy,the panel considered the following outcomes asmost important to the patient:

(1) Survival at 5, 10 and 15 years (overall sur-vival, disease-specific survival, progression-freesurvival and metastasis-free survival);

(2) Progression rates at 5, 10 and 15 years(metastatic, local and biochemical); and

(3) Complications of treatment. Although allcomplications were evaluated, the most importantare: death from treatment, incontinence, impotence(erectile dysfunction), cystitis, proctitis, majorbleeding, pulmonary embolism, rectal injury andbladder neck contracture/urethral stricture.

Survival at 5, 10 and 15 years

Clinically localized prostate cancer (stages T1and T2) is rarely lethal within the first 5 years afterdiagnosis. The overall death rate during this periodis low and usually secondary to comorbid process-es. Almost any treatment for localized prostate can-cer would appear to have an excellent survival re-sult at 5 years. Survival at 10 years and 15 years al-lows a more accurate assessment of the influence ofprostate cancer treatment on patient survival.

It is not enough to assess survival independentlyof tumor progression status. Comorbid processesassociated with advanced age will often determinesurvival. However, morbidity from cancer progres-sion may occur for years prior to death. It is there-fore reasonable to inform patients not only aboutthe risk of dying from prostate cancer, but alsoabout the risk of developing metastatic disease orany evidence of tumor recurrence during follow-up.Thus, outcomes of cancer-specific metastasis-freeand tumor-free survival should be assessed in addi-tion to overall survival rates.

Treatment alternativesand treatment outcomes



Progression rates at 5, 10 and 15 years

After surgery or radiotherapy, most recurrence orprogression of adenocarcinoma of the prostate willbecome biochemically (PSA) apparent by 5 years,but a few patients may have lengthy delays beforethe progression becomes clinically apparent. It istherefore important to continue to assess progres-sion rates to 10 years and beyond. Progression ratesmay or may not influence the patient directly. Manytimes progression will be defined as the develop-ment of any evidence of tumor. This recurrence isoften asymptomatic and found only through sur-veillance examinations.

Obviously, either local recurrence or sympto-matic metastatic prostate cancer is of extreme im-portance to patients diagnosed with localized dis-ease. However, biochemical failures, usually in theform of rising serum PSA, may also negatively im-pact patients from a psychologic standpoint. Menwith prostate cancer understand that a rising serumPSA often precedes eventual symptomatic recur-rence.

Complications and harms of treatment

Treatment-related death, the most serious ad-verse outcome from treatment of prostate cancer, isuncommon. Other adverse outcomes from treat-ment, such as incontinence, impotence (erectiledysfunction), cystitis, rectal injury and bleeding, aremore common and have variable degrees of nega-tive impact on patient well-being. The reported in-cidences and estimates of these adverse outcomesare important to a patient making decisions regard-ing treatment. Some of the complications are muchless common today than in older reports because ofnewer technology and advancements in technique.It is important to stratify the complications relativeto era of treatment. (See Appendix A, Figures A-7to A-31.)

Analysis of outcomes data fromthe literature

The panel was impressed by the massive amountof literature available on prostate cancer, but thevast bulk of the literature is not usable for extract-ing and combining data to assess treatment out-comes and develop practice recommendations. Of12,501 papers reviewed, the panel was able to re-trieve only 165 with acceptable data on outcomesfrom treatment of localized prostate cancer. (Seepage 9 for an explanation of the review process.)Moreover, in these 165 articles, there are significantdifferences among treatment series regarding such

characteristics as patient age, tumor grade and pel-vic lymph node status. For example, patients under-going radical prostatectomy are on average 3 yearsyounger than those undergoing external beam ra-diotherapy and 7 years younger than those reportedto have been followed with surveillance.

It is striking that only about one in seven patientsreported in the literature was followed even for 5years and that a very small fraction was followedfor 10 or 15 years. Estimates of important out-comes—notably survival and progression rates at 5,10 and 15 years—are likely to be inaccurate if suchsmall numbers of patients are available for analysis.

Tumor grades are relatively comparable in pa-tients treated actively (with surgery or radiation);but for patients followed with surveillance, thereare data on very few patients who have high-gradetumors. Also, there is scant information on pelviclymph node status in patients receiving externalbeam radiotherapy or followed with surveillance,leaving open the possibility of dramatic differencesin the stages of patients’ tumors.

Because of the significant differences amongtreatment series and the consequent inability tomake meaningful estimates from data available forthe treatment outcomes of patient survival and tu-mor progression, the panel concluded that it wouldbe methodologically unsound to compare treatmentmodalities directly with regard to these outcomes.Nevertheless, the panel did decide to present dataresults in the form of summary outcomes tables 3–4 (pages 25-26), as well as graphically in Figures 1–13 (pages 28-31), to show the range of outcomesdata reported for the different modalities. Theranges of frequency reported for the 25 most com-mon treatment complications are shown in Table 5(page 27). Frequency rates for the most importantof these complications are depicted graphically aswell in Figures 14–16 (page 31).

The panel generated its practice policy recom-mendations based on the outcome estimates avail-able and on panel opinion. The recommendationswere graded according to levels of flexibility basedon the strength of the evidence and the panel’s as-sessment of patient needs and preferences. Threelevels—standards, guidelines and options—are de-fined on page 8. A standard has the least flexibility.A guideline has significantly more flexibility, and

Treatment recommendations

(Continues on page 6)



Recommendations: Standards

• As a standard, an assessment of the patient’s life expectancy, overallhealth status and tumor characteristics is necessary before any treatment deci-sions can be made.

Life expectancy:Life expectancy, rather than patient age, should be the fac-tor considered in treatment selection. Therefore, the panel did not set a specificchronological cutoff point. When a man’s life expectancy is relatively long,prostate cancer can be a cause of morbidity and mortality. On the other hand,at an advanced patient age, or when life expectancy is relatively short, compet-ing hazards for mortality reduce the chance that a man will suffer from diseaseprogression or die from prostate cancer. (See U.S. Life Expectancy Table inAppendix C.)

Health status:The patient’s overall health status is the sum of all condi-tions and includes both patient and family history as well as the present stateof the patient’s well-being and the degree of any coexistent disease. There aretwo reasons to evaluate the overall health status prior to deciding on an inter-vention: (1) Overall health status influences life expectancy; (2) overall healthstatus may affect patient response to adverse events resulting from particularinterventions.

Tumor characteristics: The histologic grade and stage of the tumor shouldbe considered when assessing the potential natural history and treatment op-tions for prostate cancer. Small, well-differentiated cancers progress moreslowly and are less likely to be life threatening than large, poorly differentiatedtumors which have a greater potential to be biologically aggressive and clini-cally significant.

• As a standard, a patient with clinically localized prostate cancer should beinformed about the commonly accepted initial interventions including, at aminimum, radical prostatectomy, radiotherapy and surveillance. A discussionof the estimates for benefits and harms of each intervention should be offeredto the patient.

The panel defines radical prostatectomy to include complete removal of theprostate, vasal ampullae and seminal vesicles. The panel defines radiotherapyto include external beam and/or interstitial (brachytherapy) treatments.Surveillance is defined as periodic monitoring of the patient’s prostate cancerand its effects.

The patient should be informed that depending on his condition and initialchoice, subsequent interventions may be appropriate.

• As a standard, the patient’s preference, based on his attitude toward thecourse of the disease and the benefits and harms of the different interventions,should be considered in determining his treatment.



Recommendations: Treatment options

Options for management of localized prostate cancer include radicalprostatectomy, radiotherapy and surveillance. Radiotherapy includes ex-ternal beam and interstitial (brachytherapy) treatments. The panel consid-ers these interventions to be options because data from the literature donot provide clear-cut evidence for the superiority of any one treatment.Provided for each option, however, are a description of the patient mostlikely to benefit from the intervention and a brief summary of the inter-vention’s advantages and disadvantages.

• Radical prostatectomy:Based on the panel’s interpretation of theliterature and panel opinion, the patient most likely to benefit from radi-cal prostatectomy would have a relatively long life expectancy, no signifi-cant surgical risk factors and a preference to undergo surgery.

The major advantage of radical prostatectomy is its potential for totalremoval of the cancer and “cure” in properly selected patients. “Cure” isdefined as lifetime freedom from disease. Potential harms include urinaryincontinence and erectile dysfunction. Because the cancer may not becompletely eradicated, disease progression may occur.

• Radiotherapy: Based on the panel’s interpretation of the literatureand panel opinion, the patient most likely to benefit from radiotherapywould have a relatively long life expectancy, no significant risk factorsfor radiation toxicity and a preference for radiotherapy.

The advantages of radiotherapy are that it has a potential for cure andthat it is well tolerated in the majority of men when modern techniquesare used. Its principal potential harms include radiation cystitis and proc-titis and erectile dysfunction. Because the prostate remains in place, per-sistence and progression of the disease may occur.

• Surveillance:Based on the panel’s interpretation of the literatureand panel opinion, patients most likely to benefit from surveillance arethose with a shorter life expectancy and/or a low-grade tumor.

Benefits of surveillance for low- or intermediate-grade, localized pros-tate cancer include a lack of treatment-related morbidity with only mar-ginal compromise of disease-specific survival at 5 to 10 years of follow-up. Because the prostate is neither removed nor irradiated, progression ofthe disease is more likely to occur.



an option is the most flexible. None of the panel’srecommendations, however, fits the guideline cate-gory defined on page 8.

The standard patientThe panel’s recommendations apply to the stan-

dard patient, defined as a man who has clinically lo-calized prostate cancer (adenocarcinoma of theprostate). For this report, the panel focused on clini-cal stage T2 (B) disease. Based on the opinion ofthe panel, recommendations may also be applied topatients diagnosed with stage cT1c disease (detect-ed by elevated PSA). The recommendations werenot developed for patients with stage T1a/b (A1/A2)or clinical T3-T4 (C) disease. For a detailed discus-sion of prostate cancer staging, see pages 13-15.

Limitations in the literatureThe medical literature for stage T2 prostate can-

cer is, overall, clearly deficient in usable data onwhich to base comparable estimates for outcomesof treatments and to make practice policy recom-mendations. The deficiencies are such that the Pros-tate Cancer Clinical Guidelines Panel was unable todevelop, based on evidence from the literature,treatment-comparable outcome estimates for themost important outcomes: patient survival and tum-or progression at 5, 10 and 15 years. Major limita-tions can be summarized as follows:

• Few randomized controlled trials:Most ofthe data come from case series not subjected to therigors of a carefully performed, prospective, central-ly controlled clinical trial. Indeed, most of the stud-ies the panel reviewed in its literature search wereclinical series based on “convenience samples,” pa-tients available in the clinical setting where the re-search was done. The majority of the other limita-tions summarized on this page stem from the pau-city of randomized controlled trials.

• Insufficient data: Many articles do not reportall outcomes (such as cancer-specific, metastasis-free and tumor-free survival). Also, there are fewdata on high-grade tumors in patients managed bysurveillance, or on pelvic lymph node status in pa-tients managed by external beam radiotherapy aswell as surveillance. In another very important ex-ample, many articles do not specify ages of patients

despite the effect of age on survival and the signifi-cant differences in average patient age for differenttreatment modalities. In still another example, manyarticles reporting complications from treatment donot report “zero complications.” For instance, an ar-ticle may not refer to incontinence in its list of treat-ment-related complications. Readers are left towonder whether the complication did not occur or ifit was omitted from the report.

• Data variability: Examples of variabilityabound in the literature. For instance, staging meth-odology often varies between studies, not only withregard to clinical staging versus surgical staging,but with regard to differences in types of lymphnode dissections (not all of which are comparable).Patient populations differ greatly in the literature, asdo such important factors as means and length offollow-up.

• Publication bias:Because not all physicianspublish, case-study results may not be generallyrepresentative. Moreover, studies with negative orequivocal results are less likely to be submitted forpublication and less likely to be published if sub-mitted.

Recommendations for futureresearch

Most research needs can be grouped in three cat-egories: (1) new and better methods to diagnose andmanage localized prostate cancer; (2) prospective,randomized, controlled studies of the issues con-cerning prostate cancer, especially controlled stud-ies of competing treatments for the management oflocalized prostate cancer; and (3) studies of howprostate cancer and its treatments affect patientquality of life.

❶ In the first category,needs for new methodsof cancer diagnosis and monitoringinclude theneed for a more sensitive, more specific tumor indi-cator. As clinically useful as serum PSA values havebecome, they lack important properties such asprostate-cancer specificity.

Needed also are biochemical, radiographic and/orgenetic methods to assist in staging and to deter-mine reliably which cancers are biologically aggres-sive and which are clinically insignificant. For de-tecting potentially life-threatening cancers whilestill localized, it would be useful to have a geneticmarker that can identify men likely to develop sucha tumor in their lifetimes.

❷ In the second category,randomized, prospec-tive, controlled studiesof competing treatments formanaging localized prostate cancer are clearly a

Literature limitations andrecommendations for research



pressing need, especially comparative studies inves-tigating surveillance vis-à-vis active treatments.

Properly designed efficacy studies of treatmentmodalities will provide reliable descriptive data forthe patients studied. The descriptive factors shouldinclude age, tumor stage, tumor grade, ploidy, PSA,performance status and comorbidity, as well as costfactors and validated measures of quality of lifeover the course of a trial.

End points measured in a trial should includerisk of local recurrence, risk of disease progression(including objective measures of symptoms associ-ated with progression), risk of metastatic diseaseand risk of prostate cancer death.

Following are additional suggested study topicsand issues for each of the three major modalities:

• Radical prostatectomy:Methods of improv-ing preoperative staging, reducing the numberof patients with extraprostatic disease and re-ducing treatment complications; strategies toreduce the cost of the procedure; better waysto disseminate advances in surgical techniqueto the urologic community; treatments for pa-tients with pathologically proven (pT3) ex-traprostatic disease; and treatments for patientswith evidence of serologic (PSA) failure.

• Radiotherapy: Ways to reduce treatment mor-bidity; ways to standardize treatment; the roleof three-dimensional conformal therapy and ofradiosensitizers; strategies to reduce the costof treatment; optimal treatment at progression;mature data on long-term follow-up of existingradiotherapy patients; stage-specific complica-tions data on existing series; and PSA andbiopsy data.

• Surveillance:Optimal schedule of follow-upand optimal interventions at evidence of pro-gression.

Among the other topics and issues that need tobe addressed in rigorously designed clinical trialsare:

• New technologies for the treatment of clinical-ly localized prostate cancer;

• Trade-offs between survival and quality oflife—including analysis of methods by whichpatients make treatment choices and the roleplayed by quality-of-life factors in thosechoices;

• Opportunities for chemoprevention of prostatecancer including dietary interventions, hor-monal therapy and retinoid therapy;

• New strategies for the use of hormonal treat-ments;

• Combined therapies for prostate cancer;• Development and validation of surrogate mea-

sures of long-term prostate cancer outcomes(e.g.,validation of PSA failure as a surrogatefor cancer survival).

❸ Finally, the third category of research needsconsists of research into how prostate cancer andits treatments affect patient quality of life. Suchresearch would include the second topic in theabove list: analysis of trade-offs between survivaland quality of life and of the role played by quality-of-life factors in patients’ treatment choices.Needed as well are improved methods for involvingthe patient in a meaningful and efficient decision-making process and for providing unbiased infor-mation to patients and physicians about emergingprocesses and outcomes of care.


Page 8 Copyright © 1995 American Urological Association, Inc.

The AUA Prostate Cancer Clinical GuidelinesPanel developed the recommendations in thisReport on the Management of Clinically LocalizedProstate Cancerfollowing an explicit approach todevelopment of practice policies (Eddy, 1992). Theexplicit approach attempts to arrive at recommenda-tions through mechanisms that take into account therelevant factors for making selections from alterna-tive interventions. Such factors include estimationof outcomes from the interventions, considerationof patient preferences regarding those outcomes(including costs engendered by the interventions)and assessing when possible the relative priority ofthe interventions for a share of limited health careresources. Emphasized is the use of scientific evi-dence in estimating the outcomes of interventions.When panel opinion is necessary, the explicit ap-proach calls for an explanation of why it is neces-sary and discussion of the factors considered.

To develop recommendations for this report, thepanel made an extensive effort to review the litera-ture on stage T2 (B) prostate cancer from 1966-1993 and to estimate outcomes from the alternativetreatment modalities as accurately as possible.Unfortunately, the paucity of randomized, con-trolled trials and lack of comparability among treat-ment series regarding the most important outcomes,survival and disease progression, made method-ologically sound estimations impossible for com-paring alternative treatment modalities.

The review of the evidence began with a litera-ture search and extraction of data as described onpage 9. The data available in the literature were dis-played in evidence tables. From these tables, thepanel attempted to develop estimates of outcomesfor major treatment alternatives (radical prostatec-tomy, radiotherapy and surveillance). In Chapter 3,outcomes are analyzed in detail.

The panel generated its practice policy recom-mendations based on the outcome estimates avail-able and on expert opinion. The recommendationswere graded according to three levels of flexibilitybased on the strength of the evidence and the pan-el’s assessment of patient needs and preferences.

Levels of flexibility are defined as follows (Eddy,1992; American Academy of Family Physicians,1995):

• Standard: A policy is considered a standardif the health and economic outcomes of the al-ternative interventions are sufficiently well-known to permit meaningful decisions andthere is virtual unanimity about which inter-vention is preferred.

• Guideline: A policy is considered a guidelineif the health and economic outcomes of the in-terventions are sufficiently well-known to per-mit meaningful decisions and an appreciablebut not unanimous majority agree on which in-tervention is preferred.

• Option: A policy is considered an option if(1) the health and economic outcomes of theinterventions are not sufficiently well-knownto permit meaningful decisions, (2) prefer-ences among the outcomes are not known, (3)patients’ preferences are divided among alter-native interventions and/or (4) patients are in-different about the alternative interventions.

Standards obviously have the least flexibility.Guidelines have considerably more flexibility, andoptions are the most flexible. In this report, theterms are used to indicate the strength of the rec-ommendations. A recommendation was labeled astandard if the panel concluded that it should befollowed by virtually all health care providers forvirtually all patients. A recommendation would belabeled a guideline if the panel thought it appropri-ate not for all, but for a significant majority of pa-tients. None of the recommendations in this report,however, fits the guideline category.

Recommendations in this report regarding treat-ment choices were labeled options mostly becauseof the inability to estimate outcomes meaningfullyfrom the evidence available. Because the evidencedoes not permit direct comparison of the most im-portant outcomes among alternative treatmentmodalities, the comparative recommendations forthese modalities are presented as treatment optionsrather than as guidelines or standards (page 38).

Another reason for labeling a recommenda-tion an option is that patient preferences may be

Methods and definitions

Chapter 1: Methodology


Page 9Copyright © 1995 American Urological Association, Inc.

unknown or divided because of complications fromthe treatment, in which case it is particularly impor-tant to consider preferences of individual patients inselecting from among alternative interventions.

To extract scientific evidence about the outcomesfrom alternative interventions for treating stage T2(B) prostate cancer, the panel performed a literaturesearch utilizing the MEDLINE database. The data-base was searched several times up to December1993, using the MESH subject heading “prostaticneoplasms.” All citations recovered were importedinto a bibliographic database software system(Papyrus Bibliography System; Research SoftwareDesign, Portland, Oregon).

Members of the panel reviewed abstracts for12,501 articles on prostate cancer published from1966 to 1993. Each abstract was independently re-viewed by two panel members. If either memberthought the article appeared relevant, it was re-trieved. On the basis of abstract review, 1,453 arti-cles were retrieved. After a summary review ofthese articles, the panel found 926 of the 1,453 arti-cles (64 percent) acceptable for detailed review. Ofthe 926 articles, 396 were found relevant to stageT2 (B) prostate cancer and were accepted for ex-traction of outcomes data.

Figure A-1 in Appendix A of this report showsgraphically, by year, the number of articles the pan-el retrieved on the basis of abstract review. Evidentin this graph is the dramatic increase over time inthe number of papers published. Figure A-2 showssources of articles from the English-language litera-ture. Also see Appendix A for the bibliography inTable A-1 of sources of articles from which out-comes data were extracted. (Articles cited in thetext of this report, for referencing particular pointsdiscussed, were not necessarily among articles thepanel reviewed to extract outcomes data.)

A comprehensive data-extraction form was de-vised by the panel and staff to capture as much per-tinent information as possible from each article. Asample of the form is in Appendix B. The selectedarticles were divided among the panel members,who extracted the data to complete the form.

During the finely detailed data-extraction pro-cess, 231 of the 396 stage T2 articles were rejectedfor the following reasons: 6 percent because infor-mation on patients could not be separated accordingto treatment used; 8 percent because of updated da-ta available in a later paper; 12 percent because in-formation on patients’ cancers could not be separat-ed according to stage; 16 percent because of absentdata; 27 percent because of irrelevant data; and 31percent for other, miscellaneous reasons. The netresult was 165 articles with stage T2 outcomes dataextracted (see Appendix A, Figures A-5 and A-6).

Each of the 165 articles was reviewed and thedata extracted separately by two panel members,who then met to resolve any differences. Their re-sult was entered into a database software system(PARADOX) by staff, who also verified all data en-tries. The data were entered by series. Series in thisreport are groups of patients stratified by parame-ters such as primary treatment modality.

Subsequent to data extraction, the panel attempt-ed to follow a process in which the extracted datawould be combined by meta-analysis to yield out-come estimates for alternative treatment modalities.The meta-analytically derived estimates would thenbe arrayed in an outcomes table to compare themodalities.

Meta-analysis is a term that has been used in avariety of contexts in the medical literature. In itsmost general definition, meta-analysis is any pro-cess of utilizing the results of multiple studies todetermine a final estimate for a given parameter.For this report, the definition was restricted to in-clude only formal mathematical methods of com-bining the results of multiple studies. Various meth-ods can be used. The techniques employed dependupon the nature of the studies to be combined, thedegree to which the studies are similar and thetypes of data available. In its most restrictive defini-tion, meta-analysis includes only the classical (non-Bayesian) techniques used to combine randomizedcontrolled trials.

As noted previously (page 8), after examining atlength the data on management of localized prostatecancer, the panel had to conclude that these data donot provide sufficient evidence to allow valid com-parisons of treatments. Therefore, meta-analyticcombination by any method is inappropriate.

A major reason is that the data are from clinicalseries, and data from clinical series are frequently

Data inadequacy

Data extraction

Literature search



not comparable. Pooling such data can lead tolarge, uncharacterizable biases. In the case of pros-tate cancer, the differences between series are espe-cially significant. For example, it is known that pa-tients who are older are more likely to be found inseries on treatment by surveillance or radiation.Many studies, however, do not specify ages of thepatients. In another example, patients in nonran-domized studies will likely have different grades ofdisease. Yet, grade data are frequently not available.In still another example, stage data are sometimesbased on clinical staging and sometimes on surgicalstaging. For patients not undergoing surgery, clini-cal staging is generally used, whereas authors ofsurgical series frequently reclassify patients basedon surgical stage. This implies that nonsurgical se-ries may include more higher-stage patients.

Particularly problematic are survival and disease-recurrence data (including overall survival, disease-specific survival, recurrence-free survival and timeto recurrence). The problems include differences inreporting of follow-up, differences in methods ofreporting survival and biases in losses to follow-up.

Having determined that combining the outcomesdata from different series is inappropriate, the paneldebated several methods for displaying the data.These methods included crude combinations in anoutcomes table, graphs with outcomes and sizes ofeach study shown or simply graphs with the out-comes from each study. All of these methods havethe disadvantage that the reader might infer differ-ences for alternative treatments that cannot be justi-fied.

The panel chose the simplest forms of display(pages 25-26, 28-31). In the graphical displays, thecircles indicate the rate reported by each series foroverall survival, progression-free survival, metasta-sis-free survival or disease-specific survival. Thedata are also shown in tabular form with the mini-mum and maximum percentages reported but nomean or median estimates. The tables indicatewhether reported results are based upon actuarialcalculations (life tables or Kaplan-Meier) or wheth-er they are “actual” (observed, nonactuarial), thatis, representing a ratio of an actual number of sur-vivors over a denominator that may have some re-duction for dropouts. As noted on page 23, becausemany patients are lost to follow-up, die of unknowncauses or fail to have consistent testing or to have

the data recorded, “actual” rates might not accurate-ly represent the impact of the disease or its treat-ment in the general population. For this reason, theword “actual” when used to denote such data ap-pears in quotes.

The problems that exist with regard to data forsurvival and disease progression also exist with re-gard to data for complications of treatment. Thelack of randomized trials and differences in patientpopulations and treatment techniques frequently re-sult in data not generalizable across studies. Dif-ferences in reporting data add to the problems. Forexample, many investigators do not list all compli-cations in the results sections of their studies. Theymay list only the complications that occur. Uncom-mon complications like perioperative death are thusnot included in many studies. To use such studies ina meta-analysis combining results of multiple stud-ies, a zero rate must be assumed for complicationsnot reported. Otherwise, if data were combined on-ly from those studies where a complication occurs,the estimate of frequency of occurrence would beartificially high.

Because of the various problems with regard tothe complications data, the panel chose not to com-bine these data from the different studies in order toestimate frequency of occurrence for alternativetherapies. The panel elected instead to display thecomplications data using the same method as forsurvival and progression data. For each of the mostimportant complications, such as perioperativedeath, impotence (erectile dysfunction), rectal in-jury and incontinence, a graph indicates the report-ed frequency rates for that complication (see Fig-ures 14–16, page 31). The data are shown in tabu-lar form as well (page 27), with reported high andlow rates to indicate a range but with no mean ormedian estimates. In Chapter 3, tables and graphsare explained in detail.

The discussion sections in Chapter 2 provide pri-marily descriptive and explanatory informationabout the natural history of prostate cancer, theGleason grading system and systems and methods

Literature citations and panelopinions in discussion sections

Treatment complications data

Data display for survivaland disease progression



used for clinical staging. Also provided in Chap-ter 2 are individual overview discussions of thetreatment alternatives analyzed by the AUAProstate Cancer Clinical Guidelines Panel: radicalprostatectomy, external beam radiotherapy, brachy-therapy (interstitial radiotherapy) and surveillance.Advantages and disadvantages of each of thesetreatment options are discussed on pages 38-41 ofChapter 4, following the panel’s treatment recom-mendations.

Some of the studies cited in the discussion sec-tions in Chapters 2 and 4 are in addition to articlesreviewed by the panel for data extraction and analy-sis. Among the additional articles are papers pub-lished after December 1993. As noted on page 9,December 1993 was the cutoff date in the literaturesearch to obtain articles for the purpose of extract-ing outcomes data. However, the discussion sec-

tions also include information from more recentstudies published in 1994.

Although these discussion sections contain pri-marily descriptive and explanatory information,some sections also contain panel opinions based onevidence from studies cited in the text of the dis-cussion. In particular, the section in Chapter 2 onstaging methods (pages 13–15) contains panel opin-ions questioning the need to use methods such ascomputerized tomography (CT) scan and magneticresonance imaging (MRI) for patients with clinical-ly localized prostate cancer. Reasons for panelopinions are stated explicitly in this and other sec-tions, but it should be recognized that no attemptwas made to subject the evidence cited to a rigor-ous review process like that described on pages 9-10 of this chapter.



Chapter 2: Prostate cancer and its management

Prostate cancer is the most commonly diagnosedvisceral neoplasm in men. The estimated 244,000new cases diagnosed in the United States in 1995represent 36 percent of cancers in men, comparedto 14 percent for lung cancer and 10.4 percent forcolorectal cancer, the next two most frequently di-agnosed cancers (Wingo, Tong and Bolden, 1995).The 40,400 deaths from prostate cancer anticipatedin 1995 represent 14 percent of all cancer deaths inmen, placing prostate cancer second only to lungcancer mortality (33 percent) and ahead of colorec-tal cancer mortality (9.4 percent).

Of the malignant conditions that arise primarilywithin the prostate gland, by far the most frequentlyoccurring type is adenocarcinoma. Because of therarity of other primary neoplasms within the gland,the terms “prostate cancer” and “carcinoma of theprostate” are generally understood to be synony-mous with “adenocarcinoma.”

Anatomically, four glandular prostatic regionsare recognized: (1) the transition zone, a bilobararea lying on each side of the distal two-thirds ofthe supramontanal prostatic urethra in the unen-larged state, but which can, following the develop-ment of benign prostatic hyperplasia, occupy asmuch as 95 percent of the entire gland volume; (2)the central zone, which occupies the major portionof the cephalad half of the prostate; (3) the periph-eral zone, which occupies most of the distal half ofthe gland and (4) the periurethral glands lining theurethra.

Approximately 75 percent of prostatic carcino-mas arise in the outer gland (a combination of thecentral and peripheral zones), and many of thesecancers are multifocal. The remaining 25 percentarise in the transition zone. The volume of thelargest area of involvement, if in the peripheral orcentral zones, correlates with overall tumor stage.The periurethral glands are rarely involved in ma-lignant change.

A nonglandular area, the fibromuscular stroma,lying on the anterior gland surface as well as com-prising the internal and external urethral sphincters,

is devoid of carcinomatous change as its compo-nents do not include glandular tissue.

Prostate cancer has a wide spectrum of growthrates. Many tumors pursue a relatively indolentcourse over a number of years. Others advance rap-idly by local extension and/or metastasis. Evalu-ation of the effect of active intervention must takeinto account the course the disease would follow ifit were allowed to proceed without interference.Active treatment of a prostatic cancer that is des-tined never to present a clinical problem to the pa-tient would not be expected to improve patient out-comes over treatment by surveillance alone. Pros-tate cancer aggressiveness, however, does tend toincrease with time (Adolfsson and Tribukait, 1990).Given sufficient time, small localized tumors can beexpected to become large, multifocal, nonlocalizedtumors (Whitmore, Warner and Thompson, 1991),with decreasing likelihood of cure. “Cure” is de-fined in this report as lifetime freedom from dis-ease.

Thus, because techniques for distinguishingrapidly growing from slow growing tumors are stillevolving, patient longevity becomes a major factorin determining treatment. Treatment of prostatecancer depends to a significant degree upon the pa-tient’s age, functional level and medical status.Because a younger, healthier patient may be ex-posed to a longer period of risk for disease progres-sion, metastases and death, consideration of inter-vention rather than management by surveillancemay be more compelling in this patient. Risks fordeath from untreated disease are presented in thisreport (pages 40-41), but long-term results arepoorly understood. Of concern is a recent articlesuggesting that even low-grade tumors may have ashigh as a 55 percent likelihood of resulting in can-cer death within 15 years of follow-up (Aus, Hugo-sson and Norlén, 1994). The older patient with ashorter period at risk may have a lesser chance ofprostate cancer death. The age at which the risk of

Natural history andgrade classification

Background



cancer death reaches an “acceptable” level, so thattreatment is unnecessary, is not known.

Histologic grade is currently one of the mostcommon methods for classifying tumor aggressionlevels, and the most common system currently inuse is the Gleason grading system based on archi-tectural criteria (Gleason, 1977). A primary gradefrom 1 to 5, with 5 being the most aggressive, is as-signed to the pattern occupying the greatest area ofthe specimen. A secondary grade is assigned to thepattern occupying the second largest area. Thesetwo grades are then added to get a Gleason score,which ranges from 2 to 10. It is generally agreedthat tumors with a Gleason score ≤ 6 have lower bi-ologic aggressiveness and those with a Gleasonscore ≥ 7 are biologically aggressive tumors.

Pathologists can have difficulty, however, distin-guishing grade 3 histologic patterns from grade 4histologic patterns for assigning primary or sec-ondary grades. The distinction is important. Studiesrelating component grades to spread of cancer haveshown that metastases almost never occur withgrade 3, but occur often with grades 4 and 5 (Mc-Neal, Villers, Redwine, et al., 1990). Consequently,whereas 3 + 3 = 6 is a favorable Gleason score, 4 +2 = 6 or 2 + 4 = 6 is not. Certainly not favorableare 4 + 3 = 7, 3 + 4 = 7, 5 + 2 = 7 and 2 + 5 = 7.The value of the Gleason system may thus depend,in some cases, on the pathologist’s proper catego-rization of grade 3. Still, the system is a vast im-provement over earlier, purely descriptive attemptsat classification.

Factors such as tumor grade and volume (stage),along with evaluation of nuclear chromatin contentand nuclear roundness, allow some prediction of atumor’s biologic potential. However, at the presenttime, such factors are not fully applicable to indi-vidual patients because of the many exceptions thatexist to these predictive indices.

The natural history of untreated prostate canceris discussed in detail on pages 18-19 of this chapterin the description of surveillance as a treatment al-ternative.

Several staging systems for prostate cancer havebeen described in the literature. The two used mostoften are the Jewett-Whitmore ABCD system(Prout, 1973) and the TNM system (Beahrs, Hen-son, Hutter, et al., 1992). Table 1 provides a com-parison of the two systems. Both systems have un-

dergone modifications because of the need to ac-commodate evolving concepts of prostate cancer.

Accurate determination of tumor stage is impor-tant, in that therapy is highly dependent uponknowledge of whether or not the tumor is localizedto the gland. Clinical staging has improved in re-cent years, yet considerable inaccuracy remains.This, at times, results in understaging and, to a less-er extent, overstaging as compared with surgical orpathologic staging. This has confounded accurateevaluation of treatment modalities based solely up-on clinical staging.

Staging

Table 1. TNM and Jewett-Whitmorestaging systems

STAGE

Jewett-TNM Whitmore DescriptionTX Tumor cannot be assessedT0 No evidence of tumorT1a A1 Tumor an incidental finding at TURP in-

volving 5% or less of tissue resectedT1b A2 Tumor an incidental finding at TURP in-

volving more than 5% of tissue resectedT1c B0 Nonpalpable tumor identified because of

elevated PSAT2a B1 Tumor involves one-half of a lobe or

lessT2b B1 Tumor involves more than one-half of a

lobe, but not both lobesT2c B2 Tumor involves both lobesT3a C1 Unilateral extracapsular extensionT3b C1 Bilateral extracapsular extensionT3c C2 Tumor invades one or both seminal vesi-

clesT4a C2 Tumor invades bladder neck and/or ex-

ternal sphincter and/or rectumT4b C2 Tumor invades levator muscles and/or is

fixed to the pelvic sidewallNX Regional lymph nodes cannot be as-

sessedN0 No regional lymph node metastasisN1 D1 Metastasis in a single lymph node, 2 cm

or less at greatest dimensionN2 D1 Metastasis in a single lymph node more

than 2 cm, but not more than 5 cm atgreatest dimension, or in multiple lymphnodes none more than 5 cm at greatestdimension

N3 D1 Metastasis in a lymph node more than 5cm at greatest dimension

MX Presence of distant metastasis cannot beassessed

M0 No distant metastasisM1 D2 Distant metastasis



Methods used in clinical stagingof prostate cancer

Methods available for staging of clinically local-ized prostate cancer include digital rectal examina-tion (DRE), serum prostate specific antigen (PSA),serum acid phosphatase, transrectal ultrasonogra-phy (TRUS), computerized tomography (CT) scanand both body and endorectal magnetic resonanceimaging (MRI). For determination of distant metas-tases, staging methods include CT scan, MRI andradioisotopic bone scan. In the panel’s opinion,based on growing evidence from recent studies,many of the methods available do not necessarilyprovide useful information and may not be requiredfor patients with clinically localized prostate can-cer.

CT scan and MRI

Approximately 50 percent of patients with newlydiagnosed prostate cancer undergo a CT scanand/or MRI to assess locoregional spread (Stameyand McNeal, 1992). Yet, for most patients, thesestaging modalities provide little useful informationand may not be necessary. Capsular perforation,seminal vesicle invasion and pelvic lymph node in-volvement most often are microscopic phenomenaand, if so, cannot be diagnosed by either CT orMRI (Rifkin, Zerhouni, Gatsonis, et al., 1990).These tests can often detect gross extraprostatic dis-ease, but that degree of spread can usually be deter-mined from the serum PSA concentration, DRE orTRUS at time of biopsy. For these reasons, CT andMRI may not be required in the staging evaluationof patients with clinically localized prostate cancer.

Prostate cancer detected by PSA

Beginning in 1987, PSA has gradually achievedwidespread clinical use, initially as a tumor markerfor monitoring response to treatment, and more re-cently as an indicator of early, potentially curableprostate cancer (Brawer, Chetner, Beatie, et al.,1992; Catalona, Smith, Ratliff, et al., 1991; Cooner,Mosley, Rutherford, et al., 1990; Labrie, Dupont,Suburu, et al., 1992).

It is well established that serum PSA can identi-fy patients with prostate cancers not detectable byDRE, thus increasing the number of nonpalpableprostate cancers being diagnosed. As shown inTable 1 in the TNM staging system, “PSA-detect-ed” cancers are classified as stage T1c; in theJewett-Whitmore staging system, they are referredto as stage B0 (Stormont, Farrow, Myers, et al.,1993).

Studies indicate that most nonpalpable, PSA-de-tected prostate cancers are of sufficient volume toclassify them as clinically important (Brendler,Carmichael, Walsh, et al., 1993; Epstein, Walsh,Carmichael, et al., 1994; Oesterling, Suman,Zincke, et al., 1993; Scaletscky, Koch, Eckstein, etal., 1993). There is no evidence that PSA-detectedprostate cancers are different from small DRE-de-tected tumors.

Pelvic lymph node dissection

Pelvic lymph node dissection (PLND) has longbeen considered the gold standard in evaluation ofregional metastases from prostate cancer. AlthoughPLND can provide staging information obtainableby no other method, the procedure increases time insurgery and can increase patient morbidity. Poten-tial complications include hemorrhage, lymphocele,infection and vascular and neurologic injurieswhich occur in as many as 20 percent of those pa-tients undergoing PLND (Donohue, Mani, White-sel, et al., 1990; Kavoussi, Sosa, Chandhoke, et al.,1993).

Evidence is mounting that most patients who arecandidates for a radical prostatectomy or radiother-apy have very low risk for positive pelvic lymphnodes. One study found that patients with a primarytumor volume less than 4 cc (1.5-2.0 cm in diame-ter) do not have lymph node metastases (Stamey,McNeal, Freiha, et al., 1988). Another study notedthat only 6 of 274 patients (2 percent) with palpabledisease in one lobe (clinical stage T2a/T2b) hadpositive pelvic lymph nodes, in contrast to 23 per-cent of 84 patients with palpable disease in bothlobes (clinical stage T2c) (Walsh, 1988). The Stan-ford group found in patients with clinical stageT2a/T2b disease that no patients having sextantneedle biopsy specimens positive in only one lobehad positive lymph nodes, and only 8 percent of pa-tients having biopsy specimens positive in bothlobes had lymph node metastases (Daniels, McNealand Stamey, 1992). In two other large contempo-rary series of almost 600 patients, in which thecancers were detected using PSA screening, the in-cidence of positive pelvic lymph nodes was approx-imately 5 percent (Danella, deKernion, Smith, etal., 1993; Petros and Catalona, 1992).

In a study reviewing 1,632 patients with clinical-ly localized prostate cancer who had undergone bi-lateral pelvic lymphadenectomy at the Mayo Clinic,the overall incidence of positive pelvic lymphnodes was 12 percent (Bluestein, Bostwick, Berg-stralh, et al., 1994). Using logistic regression analy-sis, serum PSA was found to be the best predictorof pelvic lymph node metastases.



However, the predictive power of serum PSAcould be enhanced considerably by taking into ac-count the tumor grade and clinical stage. Using allthree clinical parameters together, a statistical mod-el was generated that allows the practicing urologistto accurately estimate the probability of pelviclymph node involvement. The model indicates thatwhen the serum PSA concentration, tumor gradeand local clinical stage are below certain levels, theprobability of positive lymph nodes is extremelylow. A pelvic lymph node dissection may not benecessary (Bluestein, Bostwick, Bergstralh, et al.,1994).

Radionuclide bone scan

The most sensitive method to detect bony metas-tases is radionuclide bone scan. Of late, evidencehas accumulated suggesting that bone scans may beeliminated for selected patients. Based on twolarge-scale clinical studies, Oesterling and col-leagues have determined that serum PSA concentra-tion can be used to reliably predict bone scan find-ings in patients with newly diagnosed prostate can-cer.

In the first clinical study, the investigators evalu-ated, retrospectively, 521 randomly selected pa-tients who presented with newly diagnosed, untreat-ed prostate cancer (Chybowski, Larson-Keller,Bergstralh, et al., 1991). All were evaluated with re-gard to local clinical stage as determined by DRE,biopsy tumor grade, serum acid phosphatase, pro-static acid phosphatase concentration, serum PSAand bone scan findings. Of all the clinical parame-ters available to predict the presence of skeletalmetastases, PSA was the best in predicting the re-sults of a radionuclide bone scan. For a serum PSAconcentration of 10 ng/ml or less, the probability ofskeletal metastases (positive bone scan) is extreme-ly low—less than 1.5 percent.

In order to confirm these initial findings, a sec-ond investigation was conducted to assess the abili-ty of serum PSA to predict bone scan findings(Oesterling, Martin, Bergstralh, et al., 1993).Medical records of 2,064 consecutive patients withprostate cancer were reviewed. Patients with priortreatment (androgen deprivation therapy, radicalprostatectomy or radiotherapy) were excluded. Aswith the previous study, irrespective of the tumorgrade and local clinical stage, the serum PSA valuewas the best predictor of the bone scan results.Combining tumor grade, local clinical stage or bothwith PSA did not enhance the predictive power ofPSA. This second investigation also confirmed theobservation that patients with a low serum PSA

concentration (less than 10 ng/ml) rarely haveskeletal metastases.

From the results of these two large clinical stud-ies, it appears that a staging radionuclide bone scanmay no longer be necessary for the patient withnewly diagnosed, untreated prostate cancer who hasno skeletal symptoms and a serum PSA concentra-tion of 10 ng/ml or less.

The evolution of therapeutic modalities for treat-ment of prostate cancer has been continuous overthe past several decades, making it difficult to as-sess the comparative value of each modality. Also,the treatment options for a particular patient aresubject to a number of constraints. First is an as-sessment of the patient’s life expectancy based up-on actuarial and comorbidity information, his func-tional status and his own wishes regarding therapy.Another important concern is whether the malig-nancy is believed to be confined within the gland orwhether it has spread either regionally or distantly.

The following treatment alternatives in currentuse for managing localized prostate cancer, eitheralone or in various combinations, were analyzed bythe AUA Prostate Cancer Clinical Guidelines Panel:radical prostatectomy, external beam radiotherapy,brachytherapy (interstitial radiotherapy) and sur-veillance (also known as expectant management,watchful waiting or observation).

Treatment methods that the panel considered in-vestigational are thermotherapy, cryotherapy, andro-gen deprivation and chemotherapy. A treatmentmethod was categorized as investigational if thepanel found the number of patients treated inade-quate for evaluation and/or if follow-up has beeninadequate to provide sufficiently precise outcomeestimates.

Treatment alternative: Radical(total) prostatectomy

Patient selection

Surgical removal of the prostate gland is “cura-tive” only if all the tumor is removed. “Cure” is de-fined as lifetime freedom from disease. Therefore,the appropriate patient for radical prostatectomyhas the disease clinically confined to the prostate,with no area of extension beyond the capsule or fix-ation of the gland and no evidence of regional or

Treatment alternatives



distant disease. This would include selected patientswith clinical stage T1 or T2 biopsy-proven tumors.Evidence suggests that not all of these patients needto undergo a pelvic lymph node dissection or a ra-dionuclide bone scan before radical prostatectomy(see pages 14-15).

The appropriate patient also has these character-istics: (1) an expected longevity longer than the ex-pected morbidity of his cancer if left untreated; (2)no significant surgical risk factors; and (3) a will-ingness to undergo surgery following a discussionof risks, postoperative side effects, natural historyand options (Gibbons, 1993).

Life expectancy of the patient

Although relentless, the growth pattern of inter-mediate- and low-grade prostate cancers (Gleasonscore ≤ 6) is such that the cancer might not repre-sent a significant threat to the patient in his lifetime.An assessment of the patient’s overall health statusis therefore mandatory before any treatment recom-mendations can be made. This should include infor-mation regarding age and cause of death of parents,familial longevity and diseases (for example, hyper-tension, cardiovascular, metabolic), and past andcurrent health problems.

Patients with localized prostate cancer might becandidates for treatment by surveillance or delayedtherapy if they have a low-grade tumor and a lifeexpectancy of 10 years or less (Whitmore, 1993),whereas patients with a greater life expectancymight be considered candidates for radical prosta-tectomy.

Performance of radical prostatectomy

Radical prostatectomy is performed using eitherthe retropubic or perineal approach. Walsh and as-sociates have provided considerable insight into theperiprostatic anatomy over the last 10 years, whichhas reduced the complications associated with theretropubic procedure (Walsh, 1992). Techniques in-clude precise control of bleeding from the dorsalvein complex, to allow a more precise anatomicdissection of the apex, and identifying the branchesof the pelvic plexus that innervate the corpora cav-ernosa so that they can be preserved and sexualfunction can be maintained. These “nerve-sparing”techniques have subsequently been incorporated in-to the perineal procedure (Weldon and Tavel, 1988).

The goal of both the retropubic and perineal ap-proaches is to remove the entire prostate gland,both seminal vesicles, both ampullae of the vas andthe surrounding tissues including the bladder neck.

The bladder neck opening is then contoured as nec-essary to the size of the urethral stump where anend-to-end anastomosis is performed. The princi-ples of the operations are well established, withusual operating times of 2 to 4 hours. Hospitaliza-tions of 3 to 6 days are the rule, and the patient hasan indwelling catheter for 10 to 21 days.

Treatment alternative: Externalbeam radiotherapy

Technological improvements

Advances in radiation oncology over the last sev-eral years have substantially improved externalbeam radiotherapy for prostate cancer. Technologi-cal improvements allow the radiation beam to bemore precisely targeted to the prostate and seminalvesicles, sparing normal tissues to a greater degreefrom harmful effects of radiation. Computer tech-nology now permits accurate three-dimensional de-lineation not only of the prostate and seminal vesi-cles, but of the normal rectum, bladder and otherstructures (conformal therapy). This facilitates indi-vidually customized therapeutic blocks, sharply fo-cusing the radiation beam on the target volume.

Moreover, recent advances in clinicopathologicunderstanding of the likelihood of seminal vesicleextension, the location of the prostatic apex, the im-portance of day-to-day prostate motion and thetherapeutic efficacy of lymph node irradiation haveall contributed to improvements in external beamradiotherapy. The full effects of these advances in atherapeutic context will become clearer over thenext several years as data from long-term follow-upbecome available.

Patient selection

Patients selected for external beam radiotherapyshould have a relatively long life expectancy and nosignificant factors for radiation toxicity. For in-stance, bilateral femoral hip replacements can sig-nificantly interfere with the delivery of radiothera-py. In addition, patients with systemic lupus erythe-matosis, other unusual collagen vascular diseasesand inflammatory bowel diseases such as ulcerativecolitis are candidates for an alternative therapy.

Known pelvic nodal metastasis is a strong con-traindication to external beam radiotherapy. Stud-ies by both Memorial Sloan-Kettering (Fuks,Leibel, Wallner, et al., 1991) and the RadiationTherapy Oncology Group (Hanks, Krall, Pilepich,et al., 1992) reported that only about 10 percent ofpatients with node-positive disease at presentation



remain free of disease at 10 years, and there is noindication of a plateau in the disease-free survivalcurve. This indicates that node-positive patients,with perhaps rare exceptions, cannot be cured us-ing current radiotherapy techniques and may re-quire an alternative therapy.

Patients likely to benefit most and have the bestresults from external beam radiotherapy are gener-ally those who are also ideal candidates for radicalprostatectomy. Patients with T2a tumors will havemuch better long-term disease-free survival thanpatients with T2b or T2c tumors (Glick, Philput, El-Mahdi, et al., 1990; Kaplan, Prestidge, Bagshaw, etal., 1992; Kuban, El-Mahdi and Schellhammer,1989b; Schellhammer, Whitmore, Kuban, et al.,1989). Patients with well-differentiated tumors, nor-mal acid phosphatases and PSA values ≤ 10-15ng/ml have markedly improved outcomes comparedto patients with either higher-grade tumors or high-er PSA values at time of presentation. This hasbeen well documented (Asbell, Martz, Pilepich, etal., 1989; Duncan, Warde, Catton, et al, 1993; For-man, Zinreich, Lee, et al., 1985; Landmann andHunig, 1989; Perez, Garcia, Simpson, et al., 1989;Pisansky, Cha, Earle, et al., 1993; Russell, Dunatov,Hafermann, et al., 1991).

Target volume

Historically, pelvic lymph nodes were includedin the radiation treatment volume as they wereknown to be positive in a significant percentage ofpatients. Some reports showed improved survivalwhen the lymph nodes were treated, versus historiccontrols (Bagshaw, 1984; Epstein and Hanks, 1993;McGowan, 1981); and regional nodal radiotherapywas known to be effective in other types of cancers.

However, there are many who now doubt the im-portance or efficacy of regional pelvic radiotherapy.As noted previously, the most mature reports of pa-tients with involved lymph nodes clearly indicatethat, at 10 years, the overwhelming majority willhave developed metastatic disease (Fuks, Leibel,Wallner, et al., 1991; Hanks, Krall, Pilepich, et al.,1992). Moreover, there is no evidence of a plateauin the disease-free survival curves, suggesting thatradiation to involved pelvic nodes is incapable ofcuring a meaningful number of patients. Finally,prospective randomized trials have demonstrated noadvantage to pelvic nodal radiation when comparedwith the results of prostate radiotherapy alone(Asbell, Krall, Pilepich, et al., 1988; Asbell, Martz,Pilepich, et al., 1989; Pilepich, Krall, Johnson, etal., 1986).

Whether to include seminal vesicles in targetvolume is also uncertain. Depending upon the pre-cise characteristics of the stage T2 prostate cancer,the risk of seminal vesicle invasion can vary from 5to 40 percent (Marks and Anscher, 1992; Mukamel,deKernion, Hannah, et al., 1987; Oesterling, Brend-ler, Epstein, et al., 1987). Most patients with semi-nal vesicle invasion will have minimal involvement(less than 16 percent of the gland). Yet, even in themost favorable subsets of T2 disease, it is not rarefor seminal vesicles to be significantly infiltrated bytumor.

For the majority of patients with T2 tumors, theseminal vesicles can be included in the target vol-ume with minimal added morbidity. However, thevolume of irradiated rectum will definitely increase.Also, in occasional patients, the seminal vesiclesextend laterally and posteriorly for a significant dis-tance, with consequently greater risk of morbidity.It is reasonable in such cases to carefully weigh theincreased risk of morbidity against the benefits oftreating the seminal vesicles, especially if the tumoris classified in the most favorable substages of T2disease.

Treatment alternative: Brachytherapy(interstitial radiotherapy)

Patient selection

Patient selection criteria for brachytherapy aresimilar to those for external beam radiotherapy. Ingeneral, operative mortality is low, but complica-tions are not infrequent (see Table 5, page 27). Fortransperineal ultrasound-guided implantation ap-proaches, widely variable complications have beenreported (Blasko, Ragde and Grimm, 1991; Iversen,Bak, Juul, et al., 1989; Smalley and Noble, 1992).Although some reports show negligible complica-tions, longer follow-up and other corroborative se-ries are needed (Bertermann, et al., 1991; Blasko,Ragde and Grimm, 1991; Bosch, Forbes, Prassvin-ichai, et al., 1986; Carey, Lippert, Constable, et al.,1988; Fowler, Barzell, Hilaris, et al., 1979; Iversen,Bak, Juul, et al., 1989).

Prior transurethral resection of the prostate(TURP) is a relative contraindication to prostatebrachytherapy. Because patients with prior TURPhave a much higher incidence of late urinary com-plications (Blasko, Ragde and Grimm, 1991), ex-treme caution in minimizing urethral dose is impor-tant. Extensive corpora amylacea also present a the-oretical contraindication to implantation withlow-energy radionuclides (125I and 103Pd). The high



electron density of the corpora amylacea may ab-sorb the radiation emitted from these low-energysources.

Finally, patients with high-grade tumors or withlarge tumor volume (expressed either as a volumet-ric estimate or as advanced clinical stage) are notwell suited for brachytherapy. No widely utilizedbrachytherapy techniques implant either the semi-nal vesicles or extracapsular tissue.

Techniques

Brachytherapy techniques involve two separatechoices: which type of radionuclide and whichmethod of administration. Isotopes can be chosenfrom a variety of radionuclides, taking into accountsuch factors as dosimetry scheme, half-life, type ofemission and tissue penetration. Brachytherapy mayalso be augmented by external beam radiotherapy,as well as by high-technology modifications thatare still investigational.

There are two methods of administration. In theearlier approach (1965 – 1985), the prostate was ex-posed retropubically. Then the radionuclide “seeds”were inserted by means of hand-positioning the car-rier needles, attempting to encompass the entireprostate mass by gross estimation. Several draw-backs to this method have been reported. One is in-ferior control of localized disease when comparedwith external beam radiotherapy (Kuban, El-Mahdiand Schellhammer, 1989a; Morton and Peschel,1988; Schellhammer, El-Mahdi, Higgins, et al.,1987; Schellhammer, Whitmore, Kuban, et al.,1989; Smalley and Noble, 1992).

Errors have also been documented in evaluatingprostate size, and thus in the numbering and spac-ing of seeds (Stone, Forman, Sogani, et al., 1988).Because distribution of seeds was difficult, the radi-ation dose was nonhomogeneous (Gore and Moss,1983; Kandzari, Belis, Kim, et al., 1982; Sogani,DeCosse, Montie, et al., 1979). Seeds migrated andwere usually passed out through the urethra (Som-merkamp, Rupprecht and Wannenmacher, 1988;Steinfeld, Donahue and Plaine, 1991). Finally,some authors have been concerned about the lowdoses delivered by 125I and 103Pd (Anderson andLing, 1991; Dale, 1985; Fowler, 1989, 1991; Small-ey and Noble, 1992). Data the panel extracted oncomplications of brachytherapy were based on thisearlier, retropubic approach.

The newer method of administering the radiation(1984-present) places the seeds much more precise-ly via the perineal percutaneous route. This ap-proach uses a perforated template on the perineumto position the carrying needles and transrectal ul-

trasound to monitor accurate distribution of theseeds. Anesthesia may be used, but no open surgeryis necessary. The transperineal method providesmore homogeneous delivery of the radiation dose tothe prostate, but some concern has been expressedabout adequately accessing the prostate base andseminal vesicles. More important, this method hasnot yet produced outcome results with long enoughfollow-up to be able to evaluate the potential advan-tages and risks. In the panel’s opinion, however,there is no evidence that results from the transperi-neal method are inferior to those from the retropu-bic method.

Treatment alternative: Surveillance

Basis for management by surveillance

The notion that no active treatment can be usedfor a disease process is not unusual. A classic ex-ample is the common cold. However, for such apolicy of “no active treatment” or “surveillance” tobe used for a neoplasm in which morbidity or mor-tality can occur, one or more of the following crite-ria must be met: (1) The neoplasm must have a lowrisk of morbidity and mortality; (2) The impact oftreatment upon morbidity or mortality must be neg-ligible, minimal or of unknown effect; and (3) Theharms of treatment must outweigh the benefits.

With regard to the first criterion, evidence sug-gests that low-grade, low-stage prostate canceruntreated may not produce any symptoms for pro-longed periods. Only in some patients will morbidi-ty or death from the disease ensue. Autopsies ofmen who died from other causes reveal a substan-tial number with occult prostate cancer. The rate isas high as 80 percent in older men (Franks, 1954).A study using assiduous sectioning techniques toinvestigate young men found carcinoma present in9 percent, 16 percent and 26 percent of men in theirthird, fourth and fifth decades, respectively (Sakr,Haas, Cassin, et al., 1993).

Of men with untreated prostate cancer followedup to 10 years, most series suggest that the majoritydo not die of prostate cancer but with it. Most ofthese series included older men at a higher risk ofdeath from other causes and men with less lethalforms of prostate cancer (well differentiated, lowstage). In one series (George, 1988), although 5 pa-tients died of prostate cancer, 48 died of other caus-es (4 percent versus 40 percent of the study popula-tion). In another series (Adolfsson, Carstensen andLowhagen, 1992), of the 38 percent of patients whodied, 7 percent died of prostate cancer and 31 per-cent of other causes.



In regard to the second criterion—that the impactof treatment on prostate cancer may be minor—three bodies of evidence support this contention.First, using contemporary measures of treatment ef-ficacy, many patients with clinically localized pros-tate cancer when treated for cure have been shownto be at risk for disease recurrence. In the case ofradical prostatectomy, a guiding principle holds thatif the tumor is confined to the prostate and the pros-tate is removed, likelihood of “cure” (lifetime free-dom from disease) is high. Unfortunately, the dis-ease may not, in fact, be organ confined. In theUnited States, as many as 50 percent of patients un-dergoing radical prostatectomy will be found tohave disease outside the prostate capsule or in theseminal vesicles or to have a positive surgical mar-gin (Morton, Steiner and Walsh, 1991; Wahle,Reznicek, Fallon, et al., 1990). These patients havea higher risk of disease recurrence than do patientswith organ-confined tumors (Paulson, Moul andWalther, 1990).

Some patients will be found to have a measur-able PSA following radical prostatectomy, indicat-ing persistent disease (Stein, deKernion, Smith, etal., 1992). Using PSA as an indicator of failure, pa-tients treated with radiotherapy have also been not-ed to have a high risk of relapse. One article re-ported that as many as 80 percent of patients treat-ed with radiotherapy have a rising PSA within arelatively short period of follow-up (Stamey, Ferrariand Schmid, 1993). Another article reported that ifPSA and clinical relapse are combined, the risk ofdisease relapse within 4 years following radiothera-py is 40 percent (Zagars and von Eschenbach,1993).

The second body of evidence indicates that apolicy of surveillance alone is often associated withprolonged, morbidity-free survivals. A number ofinvestigators have presented the results of a surveil-lance policy for localized prostate cancer (Adolfs-son and Carstensen, 1991; George, 1988; Johans-son, Adami, Andersson, et al., 1992; Jones, 1992;Madsen, Graversen, Gasser, et al., 1988; Rana,Chisholm, Christodoulou, et al., 1993; Stenzl andStuder, 1993; Waaler and Stenwig, 1993; Whit-more, Warner and Thompson, 1991). It must benoted that many of the patients were older and that,in many series, patients with focal disease detectedon transurethral resection of the prostate (TURP)were included (stage T1a). Nevertheless, it is in-structive to recognize that 10-year disease-specificsurvivals of between 40 and 92 percent were real-ized, with most studies in the 80 to 90 percentrange.

Finally, in a recent decision analysis, treatmentof localized prostate cancer for “cure” was calculat-ed to result in only minimal improvements in quali-ty-adjusted life expectancy (Fleming, Wasson, Al-bertsen, et al., 1993). The authors stratified patientsby age and tumor grade and made estimates oftreatment efficacy and risk of metastatic disease.Using the highest estimate of a positive effect oftreatment on life expectancy as well as the highestrisk of developing metastatic disease, the resultantincrease in quality-adjusted life expectancy was nomore than 4 years in the youngest patients studied.Using the median estimate for the risk of metastaticdisease and the highest efficacy of treatment, theauthors found that improvement of quality-adjustedlife expectancy was less than 1 year. With virtuallyall other estimates, treatment had a negative effecton quality-adjusted life expectancy.

Another study (Beck, Kattan and Miles, 1994),using more recent data from Chodak, Thisted, Ger-ber, et al. (1994), concluded that improvement inquality-adjusted life expectancy for radical prosta-tectomy compared with surveillance was 1.01, 2.41and 2.68 years for well-differentiated, moderatelywell-differentiated and poorly differentiated tumors,respectively.

The candidate for surveillance

There are two general principles in selecting theideal patient for surveillance: (1) a tumor of low bi-ologic activity (which poses the lowest threat ofmetastasis); and (2) a relatively short period of timeat risk for disease progression.

With regard to low biologic activity, tumor char-acteristics thought to be associated with the longestdisease-free survival include: low grade, low stage,low volume and (because it is often associated withtumor volume) low PSA.

As to short period at risk, because tumor pro-gression will occur in most patients with untreatedprostate cancer, given sufficient time, the ideal pa-tient for surveillance has a relatively short life ex-pectancy. Methods to estimate life expectancyinclude age (see U.S. Life Expectancy Table in Ap-pendix C), as well as information on other diseaseprocesses that the patient may have. These data canbe integrated to establish the period of time at riskfor disease progression and thereby determinewhether surveillance is an appropriate treatment op-tion.

Finally, a patient may choose surveillance formanagement of prostate cancer because of a desireto avoid or defer the side effects of other forms oftherapy.



Surveillance in practice

Following the diagnosis of prostate cancer andappropriate staging to assure that metastatic diseaseis not present, treatment alternatives are discussedwith the patient. Surveillance is presented as one ofthese treatment options. If the patient elects a pro-gram of surveillance, he is informed that the statusof his prostate tumor will be monitored periodical-ly. Monitoring may take any number of forms, butwill generally include, as a minimum, DRE andPSA. The frequency of monitoring is often basedupon a number of factors including measures of thetumor’s biologic activity (stage, grade, volume,PSA) and the age and medical status of the patient.Patients may be informed that periodic monitoringshould also include a close relationship with their

physician, including an understanding that shouldsymptoms or signs develop which the patient feelsmay be related to the tumor, he should contact thephysician at that time.

One principle of surveillance as a managementmodality for localized prostate cancer is that otherforms of intervention may be employed at any time.For example, if evidence suggests that there is aneed for further treatment, then radical prostatec-tomy, radiotherapy or other forms of therapy maybe undertaken. (The patient is then no longer a“surveillance patient.”) However, the patient mustunderstand at the outset that the delay inherent insurveillance may compromise the effectiveness ofany subsequent treatment, if any should becomenecessary.



Outcomes of therapeutic medical interventionsmay be direct or indirect. Direct outcomes affectpatients’ lives directly and are experienced directly.Some direct outcomes, such as pain from treatment,occur immediately and are short-term. Others, suchas impotence (erectile dysfunction), may occur on acontinuing basis over a period of time. Still others,such as the effect of treatment on life expectancy,can be considered future outcomes. Patient prefer-ences may differ as to relative benefits/harms be-tween different types of direct outcomes, for exam-ple, the risk of erectile dysfunction compared withthe future benefit of longer life expectancy as a re-sult of the same treatment.

Indirect outcomes are measures, such as the levelof serum PSA, that are affected by treatment butnot experienced by patients directly. Such measuresmay provide data about the probability of futureoutcomes. For example, rising PSA can be of greatimportance when assessing the effectiveness of can-cer treatment and the probability of future progres-sion of the disease.

In treating prostate cancer, differences betweendirect and indirect outcomes are less important thanin treating many other diseases. The major consid-eration is where patients place the emphasis withregard to impact on their lives. Some patients areconcerned with adverse direct outcomes such asurinary incontinence or erectile dysfunction to thepoint that they may opt for a less morbid treatment,even if the probability of “cure” (lifetime freedomfrom disease) is notably less than for the rejectedtreatment (Singer, Tasch, Stocking, et al., 1991).

However, for many men with adenocarcinoma ofthe prostate, the most compelling reason for seek-ing treatment is the hope of “cure.” Given thechoice, these men may choose the risk of inconti-nence or erectile dysfunction for an improvedchance of “cure.” They are usually well informedand recognize the prognostic implications of indi-rect measures such as rising PSA.

For assessing benefits and harms of interventionfor stage T2 (B) prostate malignancy, the AUAProstate Cancer Clinical Guidelines Panel consid-ered the following outcomes the most important tothe patient: (1) survival at 5, 10 and 15 years(overall survival, disease-specific survival, progres-sion-free survival and metastasis-free survival); (2)progression rates at 5, 10 and 15 years(metastat-ic, local and biochemical); and (3) complicationsof treatment. Although all treatment complicationswere evaluated, the most important are: death fromtreatment, incontinence, impotence (erectile dys-function), cystitis, proctitis, major bleeding, pul-monary embolism, rectal injury and bladder neckcontracture/urethral stricture.

Survival at 5, 10 and 15 yearsClinically localized prostate cancer (stages T1

and T2) is rarely lethal within the first 5 years afterdiagnosis. The overall death rate during this periodis low and usually secondary to comorbid process-es. Almost any treatment for localized prostate can-cer would appear to have an excellent survival re-sult at 5 years. Survival at 10 years and 15 years al-lows a more accurate assessment of the influence ofprostate cancer and its treatment on patient sur-vival.

It is not sufficient to assess survival independent-ly of tumor progression status. Comorbid processesassociated with advanced age will often determineoverall survival. However, morbidity from cancerprogression may occur for years prior to death. It istherefore reasonable to inform patients not onlyabout the risk of dying from prostate cancer, but al-so about the risk of developing metastatic diseaseor evidence of tumor recurrence. Outcomes of dis-ease-specific, progression-free and metastasis-freesurvival should be assessed in addition to overallsurvival rates.

Progression rates at 5, 10 and15 years

After surgery or radiotherapy, most recurrence orprogression of adenocarcinoma of the prostate will

Types of outcomes

Chapter 3:Outcomes of treatments for localized prostate cancer



become biochemically (PSA) apparent by 5 years,but a few patients may have lengthy delays beforethe progression becomes clinically apparent. Thus,it is important to continue to assess progressionrates to 10 years and beyond. Progression rates mayor may not influence the patient directly. Manytimes progression will be defined as the develop-ment of any evidence of tumor. This recurrence isoften asymptomatic and found only through sur-veillance examinations.

Obviously, either local recurrence or sympto-matic metastatic prostate cancer is of extreme im-portance to patients diagnosed with localized dis-ease. However, biochemical failures, usually in theform of rising serum PSA, will also negatively im-pact patients from a psychologic standpoint. Menwith prostate cancer understand that a rising serumPSA often precedes eventual symptomatic recur-rence.

Complications and harms oftreatment

Death from treatment is the most serious (thoughuncommon) immediate adverse outcome for a pa-tient diagnosed with prostate cancer. Other adverseoutcomes from treatment, such as incontinence, im-potence (erectile dysfunction), cystitis, rectal injuryand bleeding, are much more common and havevariable degrees of negative impact on patient well-being. The reported incidences and estimates ofthese adverse outcomes are important to a patientmaking decisions regarding treatment. Some of thecomplications are much less common today than inolder reports because of newer technology and ad-vancements in technique. It is therefore importantto stratify the complications relative to era of treat-ment. (See Appendix A, Figures A-7 to A-31.)

Cost, inconvenience and indirectquality-of-life issues

Although such issues as cost and inconvenienceare important, no meaningful data are readily avail-able from the literature. These are areas in need offuture research (see Chapter 5, page 45).

The panel was impressed by the massive amountof literature available on the topic of prostate can-cer. However, as discussed in Chapter 1 and in theLimitations section (page 42) of Chapter 5, the vast

bulk of the literature is not usable for extracting andcombining data to assess treatment outcomes anddevelop comparative estimates for these outcomes.

Of 12,501 papers reviewed, the panel was able toretrieve only 165 with acceptable data on outcomesfrom treatment of localized prostate cancer. (Seepage 9 for a discussion of the review process.)Moreover, in these 165 articles, there are significantdifferences among treatment series regarding suchcharacteristics as patient age, tumor grade andpelvic lymph node status. The differences are sum-marized in Table 2 (page 23).

Table 2 makes clear that patients receiving thevarious forms of treatment are not similar. For ex-ample, patients undergoing radical prostatectomyare on average 3 years younger than those undergo-ing external beam radiotherapy and approximately7 years younger than those reported to have beenfollowed with surveillance.

It is also striking that only about one in sevenpatients reported in the literature was followed evenfor 5 years and that a very small fraction was fol-lowed for 10 or 15 years. Estimates of importantoutcomes, particularly of survival and progressionrates at 5, 10 and 15 years, are likely to be inaccu-rate if such small numbers of patients are availablefor analysis.

Tumor grades are relatively comparable in pa-tients treated actively (by surgery or radiotherapy);but for patients followed with surveillance, thereare data on very few patients who have high-gradetumors. In addition, there is scant information onpelvic lymph node status in patients receiving ex-ternal beam radiotherapy or followed with surveil-lance, which leaves open the possibility of dramaticdifferences in the stages of patients’ tumors.

Because of the significant differences in the liter-ature among treatment series and the consequent in-ability to make meaningful estimates from availabledata for the most important outcomes, those of pa-tient survival and tumor progression, the panel con-cluded that it would be methodologically unsoundto compare treatment modalities directly with re-gard to survival and progression.

Nevertheless, in order to show the range of out-comes data reported for the different modalities, thepanel decided to display results of the data extract-ed. Results are displayed in summary outcomes

Summary outcomestables and graphs

Variability of outcomes data



tables for survival and tumor progression at 5, 10and 15 years. For survival at 5, 10 and 15 years, theresults are displayed graphically as well.

Summary outcomes tablesThe tables indicate the range of the outcomes da-

ta reported by showing highest and lowest resultsreported (maximum and minimum percentages).Because combining data among series was not pos-sible, given their variability, the panel elected not topresent summary statistics (mean or median val-ues).

The panel also decided to identify “actual” (ob-served, nonactuarial) data separately from actuarialdata and to report them separately. Although actuar-ial reporting is regarded as a more reliable way topresent treatment outcomes for men with localizedprostate cancer, the data from series reporting “ac-tual” data were also retained for review.

The major problem with actual reporting of out-comes is that prolonged follow-up is required tocollect adequate data. Some reports include cohortsof men with a minimum of 5-, 10- or 15-year fol-low-up. Knowing the outcomes for each patient in aseries for the entire follow-up time (5, 10 or 15years) has the advantage that the data are indeed ac-tual, in contrast to actuarial estimates. Unfortunate-ly, the long-term systematic follow-up needed toaccurately record these data is exceptionally diffi-cult. Patients are often lost to follow-up or die ofunknown causes, or they fail to have consistent test-ing or to have the data recorded so as to accuratelyassess disease status. Moreover, for later end points(such as 15-year disease-specific survival), thenumber of patients available by then is usuallysmall, further weakening the statistical significanceof the reported outcomes. For these reasons, theword “actual,” when used to denote “actual” data,appears in this report in quotes.

Table 2. Variability of characteristics in series1 reporting stage T2 prostate cancertreatment outcomes

TYPE OF TREATMENT

Radical External beamSeries characteristic prostatectomy radiotherapy Brachytherapy SurveillanceMean age of patients 62.7 65.9 64.5 70

(range: 34-84) (range: 26-92) (range: 36-91) (range: 38-90)Number of patients 9,263 14,205 4,891 913Number with 5-year follow-up 1,188 (13%) 1,802 (13%) 642 (13%) 400 (44%)Number with 10-year follow-up 759 (8%) 110 (1%) 100 (2%) 46 (5%)Number with 15-year follow-up 530 (6%) 0 0 33 (4%)Mean follow-up 70.2 months 70.3 months 56.5 months 111.6 months

(range: 1-372) (range: 1-264) (range: 1-219) (range: 3-298)Tumor grade: well 23.1% 41.2% 38.3% 62.2%differentiated2 (376/1,631) (517/1,256) (427/1,116) (250/402)

Tumor grade: moderately well 56.9% 40.6% 51.3% 34.8%differentiated2 (928/1,631) (510/1,256) (572/1,116) (140/402)

Tumor grade: poorly 20% 18.2% 10.5% 3%differentiated2 (327/1,631) (229/1,256) (117/1,116) (12/402)

Number with PLND 83% 26% 87% 0(910/1,093) (463/1,756) (1,743/1,997)

Series published in 1960’s 5 0 0 0Series published in 1970’s 6 9 2 0Series published in 1980’s 21 41 22 0Series published in 1990’s 23 23 11 6

1 The term “series” here denotes groups of patients stratified by parameters such as primary treatment modality. One article may have more thanone series. Table 2 data are from 169 series in 165 articles.

2 Grading system: Categorization of degree of differentiation is based either on series reports of good, moderate or poor differentiation or on thedivision of Gleason sums into 2-4 (well differentiated), 5-7 (moderately well differentiated) or 8-10 (poorly differentiated).



Actuarial reporting allows earlier analysis of datasets by using all the information in the database toestimate or predict longer-term outcomes. As morepatients survive to the desired end points (5, 10 and15 years), the confidence intervals for these esti-mates become narrower. Such a data set is dynamicand more prospective, which eliminates some of theproblems inherent in “actual” data.

A criticism of actuarial data is the inability topredict behavior of cancer for a large number of pa-tients based on the outcomes for a few. Also, thevalidity of long-term patient outcomes depends inpart on the number of patients available withlengthy follow-up. This type of quality assessmentwithin actuarial data sets was rarely stated in thepublications the panel reviewed during the literaturesearch.

For both “actual” and actuarial data, the summa-ry outcomes tables show the number of series in or-der to allow reviewers to estimate the degree towhich the data are verifiable. The number of series,however, is not the number of independent papersor reports. As used here, “series” are groups of pa-tients within a report stratified by parameters suchas primary treatment modality or stage of disease.One report may have more than one series.

These series may be subsets of clinical stage T2(B) disease. For instance, if a report classified out-comes within the stage B category according toclinical stage B1, B2, etc., and reported these dataseparately, by each substage, the panel left the dataas separately recorded rather than attempting tocombine outcomes. Therefore, under the broadercategory of stage B, there is more variability de-pending upon substages reported.

For Table 3 (page 25), which displays survivaloutcomes data, the outcomes are stratified by over-all, progression-free, metastasis-free and disease-specific survival. This stratification is necessary tocapture and record the major outcomes as reported.However, definitions of these survival subgroupsare not standardized in the literature. The terms areused by different authors with some variability intheir meaning. For this report, the panel used thefollowing general definitions:

• Overall survival: Percent of men alive, irre-spective of their disease status or the cause ofdeath in those men not alive.

• Progression-free survival: Percent of menalive without evidence of disease progression(usually overall survival minus those men whoare alive, but with progressing or recurrent dis-ease).

• Metastasis-free survival: Percent of menalive without evidence of metastatic disease(overall survival minus those men who arealive, but have metastatic prostate cancer).

• Disease-specific survival:Percent of menwho have not died from prostate malignancy(overall survival plus those men who diedfrom causes other than prostate cancer).

For Table 4 (page 26), displaying failure/progres-sion outcomes data, the outcomes are stratified bytypes of progression: local, distant, biochemical andtotal. Prostate cancer recurrence, or disease pro-gression, is reported in the literature independent ofsurvival. For the data-extraction process, the panelattempted to record the rate of progression or fail-ure as a percentage. This percentage was either cal-culated or extracted from the article’s text, tables orgraphs. If the percentage was calculated, it repre-sents the number of men who experienced or werefound to have progressing cancer, or were found tohave new evidence of cancer after or while underthe chosen therapy—as compared with the totalnumber of men being monitored.

Progression rates were assessed at 5-, 10- and15-year intervals. Definitions of progression arevague and vary from paper to paper. For this report,the panel defined categories of progression as fol-lows:

• Local: Recurrent malignancy in the prostateor prostate bed. It may vary from tumor onrandom biopsies to symptomatic cancer re-growth.

• Distant: Radiographic evidence of cancer atsites away from the prostate area. Bone andlymph nodes are the most common. Some old-er studies used plain films and serum acidphosphatase to determine distant disease.

• Biochemical: Prostate specific antigen (PSA)at present is the most reliable means to deter-mine prostate cancer recurrence, and contem-porary reports are using PSA levels alone todefine cancer recurrence. The level of PSA andrate of rise that constitute biochemical failurehave not yet been defined.

• Total: Any evidence of local or distant or bio-chemical recurrence. Adding local to distantwill not suffice since they may be present con-currently.

(Continues on page 32)



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Circle graphsSupplementing the tables is a graphical presenta-

tion consisting of “circle graphs” for 5-, 10- and15-year survival (overall, progression free, metasta-sis free and disease specific) (see Figures 1 – 13,pages 28–31). The graphs represent actuarial dataonly. In each graph, the result (percentage at 5, 10or 15 years) for one series is represented by a smallcircle at the corresponding point. Whereas the ta-bles give the number of series and maximum andminimum percentages reported, the graphs alsoshow how the reporting series are distributed overthis range. It is important to note, however, thatgraphs do not show either the size of each series orthe confidence interval for the indicated percentage.

The literature the panel reviewed to extract out-comes data for this report is quite heterogeneous. Itcovers nearly 30 years of medical history and con-tains data from studies representing countries inEurope, Asia, Africa and the Middle East as well inthe Western Hemisphere. In part because of the het-erogeneity, methods of reporting are variable—tothe extent that data reported are not sufficientlycomparable to provide a sound basis for estimatingand comparing treatment outcomes. This is dis-cussed at length in Chapter 1 (Methodology), earli-er in this chapter (pages 22-24) and in the limita-tions section (page 42) of Chapter 5.

Nevertheless, results displayed in the summaryoutcomes tables do provide some interesting, albeitinconclusive, information regarding major out-comes of treatments for localized prostate cancer.The following analysis examines the results dis-played for 5-, 10- and 15-year survival (Table 3,page 25) and for 5-, 10- and 15-year progression orrecurrence/failure (Table 4, page 26).

5-year survival resultsFor 5-year survival, Table 3 shows that more ra-

diotherapy series reported actuarial outcomes thanreported “actual” outcomes, whereas more prosta-tectomy series reported “actual” numbers than re-ported actuarial statistics. These imbalances do notappear to be important in patients who underwentexternal beam radiotherapy since the “actual” andactuarial outcome results do not differ significantly.However, significant differences between “actual”and actuarial results were evident in series of pa-

tients treated with radical prostatectomy or brachy-therapy.

Table 3 also shows a tendency toward excellentactuarial disease-specific 5-year survival results forall modalities. In general, the literature would ap-pear to support the premise that, for men with lo-calized adenocarcinoma of the prostate, disease-specific survival outcomes tend to be quite good re-gardless of treatment at 5 years, and that follow-upof 10 years or longer is needed to evaluate treat-ment efficacy with regard to preventing death dueto prostate cancer.

The reported ranges between upper and loweractuarial disease-specific results (maximum andminimum percentages) are similar for each modali-ty. External beam radiotherapy has the widestrange, which probably reflects the fact that only 26percent of patients (463/1,756) underwent a stagingpelvic lymph node dissection (PLND). (See TableA-3 in Appendix A).

The proportion of patients undergoing PLNDwas inconsistent from series to series. The fact thatfew patients in the external beam radiotherapy se-ries received PLND likely resulted in understaging.This could account for the reduced disease-specific5-year survival rate of 63.5 percent at the low endof the range, compared with close to 90 percent atthe low end for the other treatment modalities. Forprostatectomy and brachytherapy, 83 percent and87 percent of the patients, respectively, were stagedwith PLND before treatment (Table A-3).

In the three series reporting 89 to 99 percent dis-ease-specific survival at 5 years for men followedby surveillance, the very good outcome may in partbe due to the favorably high proportion of men withlow- and moderate-grade malignancy. Only 3 per-cent of men treated by surveillance had high-gradetumors, compared with 20 percent, 18 percent and10.5 percent, respectively, for the series reportingon prostatectomy, external beam radiotherapy andbrachytherapy. Men under surveillance were alsoolder at diagnosis (see Table 2 on page 23), placingthem at increased risk of death from any cause(overall survival). Although age generally affectsoverall survival negatively, advanced age may helpto explain the favorable disease-specific survivaloutcome for surveillance, compared to some inter-ventional therapy groups. Older men, at greater riskof dying from “natural” causes, are at risk for ashorter time of dying from prostate malignancy.

Progression-free survival is more variable thandisease-specific survival among treatment choices.In the radiation literature, a wide range of outcomesis reported. This is reflected in Table 3, in the wideranges shown between the lowest and highest

Analysis of summaryoutcomes tables



reported results: from 32 to 93 percent for progres-sion-free survival following treatment with externalbeam radiotherapy and from 38 to 90 percent afterbrachytherapy.

Such variability for progression-free survival isan indication of the uncertainty found in the pub-lished reports. This uncertainty is due in part to dif-ferences in intervals between follow-up and differ-ences in defining and recording progression statis-tics. The definitions vary from symptomatic localdisease to occult malignancy found on randomposttreatment biopsy. More recently, PSA has beenused to assess patients for cancer recurrence be-cause increases in serum PSA generally predateclinical evidence of progression.

The progression-free status at 5 years for mentreated with radical prostatectomy is less variable(81.9 to 92 percent actuarial, 63.6 to 91 percent“actual”) than for men managed by radiotherapy orsurveillance. This is partly due to more consistentmeans of defining recurrence. Without the prostatein place, the variability associated with posttreat-ment prostate biopsy and palpable prostatic pro-gression is reduced.

Metastasis-free survival is less subjective thanprogression-free survival, and outcome resultswould likely be more comparable between groups.However, as Table 3 shows, the treatment dataavailable did not permit evaluation of metastasis-free survival except in a limited number of externalbeam radiotherapy studies.

10-year survival resultsConsiderably fewer papers reported 10-year sur-

vival than reported 5-year survival. In most of thepapers reporting 10-year actuarial overall survival,as Table 3 makes clear, the range of outcomes wasquite similar across modalities (radical prostatec-tomy, external beam radiotherapy and surveillance).The few modest differences may be explained bythe effect of age differences.

For progression-free survival, the 10-year actuar-ial results appear excellent following radical prosta-tectomy, but only one series had extractable data.Six series reported “actual” data for radical prosta-tectomy. The results shown are variable (31.3 to 69percent), the wide range reflecting the uncertaintyof the data. Similar uncertainty is noted for the 10series reporting actuarial data for 10-year progres-sion-free survival after external beam radiotherapy(40 to 64 percent). The seven series reporting 10-year progression-free survival in men receivingbrachytherapy had the greatest variability (50 to 90percent). For men whose cancers were managed by

surveillance, only one series contained 10-year pro-gression-free survival data. Since all patients in thisseries had prostate cancer that went virtually un-treated, the progression-free percentage obviouslydepends upon how one defines “progression.” Ingeneral, the variability in 10-year outcomes illus-trates the pitfalls of attempting to compare progres-sion-free survival data from retrospective studies.

Reporting of 10-year disease-specific survivaldata is less subjective, as reflected in more uniformoutcomes and in more closely packed data points inthe graphical displays, although the latter may bemore a reflection of the small number of data points(Figures 10-13, pages 30-31). The actuarial disease-specific survival results shown in Table 3 slightlyfavor prostatectomy (86 to 93 percent). However,the less favorable results shown for external beamradiotherapy are likely affected by clinical under-staging without pelvic lymph node dissection. Thefavorable results for the three surveillance seriesmay be partly due to careful selection of patientsplaced on the surveillance protocol. Also, becauseof advanced age and shorter natural life expectancy,the time these patients were at risk for dying ofprostate cancer was less than that for younger men.As noted previously on page 32, this obviously af-fects disease-specific survival data positively, justas it affects overall survival data negatively.

15-year survival resultsThe 15-year overall survival data would appear

uncertain following prostatectomy and surveillance,as indicated by the variable results shown in Table3, with wide ranges between high-end and low-end(maximum and minimum) percentages. These data,however, are from a limited number of studies, andthe four reported series under surveillance actuallyrepresent only two studies. Three of the four “se-ries” are from stratified cohorts of patients within asingle study (Number 9351, Appendix A, Table A-1). Stratification was based on substages of stageT2 (B) prostate cancer. The 67 percent shown as amaximum percentage for surveillance representsjust the substage B1 data. For external beam radio-therapy, the relatively low overall survival results at15 years represent data from two separate, large ac-tuarial studies.

Both actuarial and “actual” disease-specific sur-vival data from reports of men receiving prostatec-tomy indicate a high likelihood of disease-specificsurvival for as long as 15 years following surgery(55 to 93 percent actuarial, 63 to 90 percent “actu-al”).



5-year progression resultsFor local progression (or disease recurrence or

treatment failure), the problem of inconsistent defi-nitions invalidates most comparisons of outcomedata between treatment options. In the case of pros-tatectomy, surprisingly few studies provide localprogression outcome data that can be meaningfullyextracted. The 5-year local progression rate follow-ing prostatectomy, as shown in Table 4, page 26,ranges widely from a low of 1.8 percent (“actual”)to a high of 11.3 percent (actuarial). The progres-sion usually includes any palpable or biopsy-proventumor in the prostatic bed or vesicourethral anasto-mosis.

Distant or metastatic recurrence at 5 years fol-lowing prostatectomy is uncommon (1.2 to 4.0 per-cent). For total 5-year clinical recurrence followingprostatectomy, the rate ranges from 3 to 12 percent(“actual”). For total progression, the panel excludeda subset in one of the studies (Number 9175, TableA-1). This subset consists of stage T2 (B) prostatecancer patients separated by deoxyribonucleic acid(DNA) ploidy pattern. The small population of 10patients (4 percent) with aneuploid tumors experi-enced 40 percent metastatic recurrence at 5 years.

For biochemical progression, local or otherwise,the panel at the time of the literature review couldfind only one study with extractable data regardingPSA recurrence (Number 10790, Table A-1). Thisstudy was in the external beam radiotherapy litera-ture. The biochemical failure rate in the study wasdefined as “increasing PSA after treatment.” Otherdefinitions have been proposed, and certainly moredata are needed to substantiate this definition.

For 5-year local progression following externalbeam radiotherapy, the actuarial rates in Table 4range from 0 to 29 percent. The true rate is obvi-ously uncertain, which again may be due in part tovariable definitions of this outcome: symptomaticdisease, palpable growth, prostate biopsy, etc.

The distant progression rate at 5 years followingexternal beam radiotherapy is also variable and un-certain. An actuarial rate of 3.8 percent reported inone study represents a group of 26 men with clini-cal stage B1 and B2 disease followed both by radia-tion oncologists and by urologists in three differenthospitals (Number 6364, Table A-1). The follow-upstudies did not specify routine bone scans or serumacid phosphatase to assess distant progression.Also, the period of follow-up ranged from 6 monthsto 8 years (median 32 months), and the authors didnot report the number of men with stage B diseasewho were followed for at least 5 years.

The 5-year total progression rates after externalbeam radiotherapy are variable as well, reflectingboth varying definitions of progression and selectedreporting of cohort outcomes. For brachytherapy,progression data reveal similar variability. Differingdefinitions of progression, technical variability andselection bias are the main reasons.

For surveillance, it can be assumed that all un-treated prostate malignancies will grow, althoughoften slowly. Therefore, progression rates on a bio-chemical or histologic basis are 100 percent in pa-tients under surveillance. However, clinically im-portant local progression during surveillance is sub-jectively reported among investigators. Forinstance, one study published a 5-year local pro-gression rate of 65 percent (95/146) for surveillance(Number 8990, Table A-1). Progression was definedas palpable local growth of tumor, and the datawere corrected to reflect cumulative probability at 5years. By comparison, another study reported a 24percent local progression rate, but defined localprogression as “a change in local tumor category”(Number 9351, Table A-1). Distant progressionrates for all studies are less subjective, as reflectedby more consistent outcomes reporting in Table 4.

10-year progression resultsThe same problems of variability in definitions

of progression, selection bias and inaccuracy in 5-year progression data are problems in data for long-er follow-up. Nevertheless, it is apparent from indi-vidual reports that the incidence of disease progres-sion/treatment failure, local or distant, does risewith time. The extracted 10-year clinical failure da-ta reflect rates that are nearly double 5-year ratesfor both radical prostatectomy and external beamradiotherapy.

However, no inference can be made from the 10-year total progression/failure rates shown in Table4. These results range too widely, reflecting highlyvariable and uncertain data as well as differing pa-tient populations.

15-year progression resultsToo few studies of 15-year outcomes are avail-

able to reasonably estimate failure rates. The datapresent in these few studies, however, indicate astabilization of local and distant progression ratesafter 10 years for men treated with either radicalprostatectomy or external beam radiotherapy. Therates continue to rise as expected for patients man-aged by surveillance. A relatively high distant fail-ure rate is reported in three series of men treated



with brachytherapy. The three series are from thesame report (Number 9879, Table A-1) and repre-sent substages of stage T2 (B) prostate cancer. Pro-gression/failure of 64 percent was found in menwith substage B3 prostate malignancy. It is obviousthat the 15-year progression data are sparse, vari-able and uncertain.

The variability in the prostate cancer treatmentliterature in reporting factors such as grade, stageand age of the patient—which has a confoundingeffect on reported data for survival and progres-sion—has a similar confounding effect on reporteddata for complications from surgery or radiationtreatment. The panel chose therefore to display re-sults of the extracted data on treatment complica-tions in the same manner as for the survival andprogression data.

The complications summary outcomes table(Table 5) on page 27 lists the 25 most commonlyreported complications. Under each treatment mod-ality to which a particular complication applies,Table 5 displays the number of series reporting thecomplication and the lowest and highest reportedfrequencies of occurrence (minimum/maximumpercentages). The table does not show mean or me-dian estimates of frequency.

Graphical displays visually represent the report-ed frequency rates for the most important complica-tions (Figures 14 - 16, page 31). Each circle on agraph represents one series reporting the complica-tion. As in the graphs representing survival out-comes, these graphs are a useful supplement toTable 5 in that they show how the reporting seriesare distributed along the range between the mini-mum and maximum percentages. Again, however, itmust be noted that the graphs show neither the sizeof each series nor the confidence interval for the in-dicated percentage.

It should also be noted that the data displayed inTable 5 and Figures 14– 16, in addition to beingsubject to problems of variability mentioned previ-ously, may be subject to publication bias. The pos-sibility exists that those centers publishing their re-sults are mainly centers having low complicationrates. The data could also be biased in the other di-rection because many of the series may not be re-cent enough for reported complications to reflect

improvements in modern surgical and radiologicaltechniques.

Some of the complications in Table 5 apply to allthree treatment modalities, but not necessarily tothe same extent. Stress incontinence, for example,is reported by 19 series as a complication of radicalprostatectomy, but by only two series as a compli-cation of external beam radiotherapy. To a consider-able degree, each form of therapy has its own spec-trum of complications. In an obvious example,wound infection is a potential complication of pros-tatectomy, but is reported by zero series under thenoninvasive external beam radiotherapy. For procti-tis, a potential complication of radiotherapy, Table5 shows a zero under prostatectomy. The panel wasunable to determine that any one therapy has amore significant cumulative risk of complications.

In the case of complications from external beamradiotherapy, the data shown in Table 5 may over-state the frequency of some complications follow-ing this treatment, such as proctitis and other rectaltoxicity. The reason is that, in abstracting the com-plications data for external beam radiotherapy, thepanel found very little information specific to stageT2 (B) disease. The panel faced a choice: either in-clude only series that purely address T2 patients, inwhich case there would essentially be no data, orinclude radiotherapy series that describe complica-tions in all stages of disease. The panel chose to in-clude all radiotherapy series that describe toxicityin order to provide at least rough indications of riskfrom therapy.

However, toxicity from radiotherapy is muchmore likely in advanced stages of disease, becausepatients reported with stages T3-T4 (C) or M1 (D2)tumors are much more likely to have received ra-diotherapy to regional lymph nodes. Radiation tothe entire pelvis and in some cases the para-aorticregion is often administered in those with higher-stage disease. Moreover, these patients are oftentreated with significantly greater doses of radiationto significantly larger amounts of normal tissue,which markedly increases toxicity (Green, Gold-berg, Goldman, et al., 1984; Lawton, Won, Pile-pich, et al., 1991; Mameghan, Fisher, Mameghan,et al., 1990; Pilepich, Krall, Sause, et al., 1987;Smit, Helle, van Putten, et al., 1990).

If the panel had been able to include only thecomplications data for external beam treatment ofstage T2 disease, the frequency rates would verylikely have been less than what Table 5 shows.Patients clinically judged as having T2 disease (as agroup) will generally receive a lower dose of radia-tion to a smaller volume of tissue.

Treatment complicationssummary outcomes table

and graphs



Of the complications listed in Table 5 for treat-ments of stage T2 prostate cancer, the panel consid-ered the most important to be perioperative death,major bleeding, pulmonary embolism, inconti-nence, impotence (erectile dysfunction), rectal in-jury, cystitis, proctitis, bladder neck contracture andurethral stricture. Most often reported are rates ofdeath, incontinence, rectal injury and impotence.Some surgical series also comment on adverse post-operative events such as bleeding and pulmonaryembolism.

A structured review of the literature (Wasson,Cushman, Bruskewitz, et al., 1993) found reportedcomplication rates within the ranges reported inTable 5. Also, patient attitudes about the impor-tance of such adverse events are now under activeinvestigation. One study used standardized data col-lection instruments to examine patient attitudes re-garding complications following radical prostatec-tomy (Fowler, Barry, Lu-Yao, et al., 1993). Reportsby these patients indicated higher rates of strictureand incontinence than in most reported series.Moreover, complete incontinence, bladder neckcontracture and stricture formation may result fromadditional interventions to ameliorate the originalproblem. Patient interviews in the Fowler study in-dicate that treatment of these urinary complications,with associated symptoms such as frequent urina-tion, wetness and difficulty in voiding, is often notvery successful. (Age was not related to postsurgi-cal incontinence in this study.)

Table 5 shows that both obstruction and inconti-nence may be more common following surgery.Cystitis, which most often results in the symptomof urinary frequency, is a potential complication ofradiotherapy. Radiotherapy is also more likely thansurgery to cause bowel/rectal injury. Diarrhea asso-ciated with radiotherapy is usually transient.

With regard to the important complication of im-potence (erectile dysfunction) following activetreatment for prostate cancer, the reports are diffi-cult to interpret because of patient selection. This isan instance in which a patient-related factor, age,may affect the complications data. The youngest(and presumably most potent) patients tend to un-dergo surgery. The oldest patients tend to receiveradiotherapy. Few reports have carefully comparedpretreatment and posttreatment potency. For treat-ment of erectile dysfunction, patients report favor-ably on treatment with pharmacologic erection ther-apy, penile implantation or vacuum devices (Fowl-er, Barry, Lu-Yao, et al., 1993).

With regard to perioperative mortality, deathfrom treatment is relatively rare following externalbeam radiotherapy. Death following surgery, al-though shown to increase with age, is generally lessthan 1 percent in men under age 75 (Lu-Yao,McLerran, Wasson, et al., 1993).

Significant bleeding may be expected to occurfollowing radical prostatectomy with a frequencybetween 1.0 and 11.5 percent. The perineal ap-proach may have the lowest incidence of this com-plication. Finally, pulmonary embolism and sepsisare risks of any operative intervention. Medicaredata suggest that the incidence of cardiopulmonarycomplications following radical prostatectomy in-creases to more than 7 percent in men over age 75(Lu-Yao, McLerran, Wasson, et al., 1993).

Analysis of treatmentcomplications summary

outcomes table



The AUA Prostate Cancer Clinical GuidelinesPanel generated its practice policy recommenda-tions based on the outcome estimates available andon panel opinion. As explained in Chapter 1, therecommendations were graded according to threelevels of flexibility based on strength of evidenceand the panel’s assessment of patient needs andpreferences. The definitions of these three levels arerepeated below from Chapter 1:

• Standard: A policy is considered a standardif the health and economic outcomes of the al-ternative interventions are sufficiently well-known to permit meaningful decisions andthere is virtual unanimity about which inter-vention is preferred.

• Guideline: A policy is considered a guidelineif the health and economic outcomes of the in-terventions are sufficiently well-known to per-mit meaningful decisions and an appreciablebut not unanimous majority agree on which in-tervention is preferred.

• Option: A policy is considered an option if(1) the health and economic outcomes of theinterventions are not sufficiently well-knownto permit meaningful decisions, (2) prefer-ences among the outcomes are not known, (3)patients’ preferences are divided among alter-native interventions and/or (4) patients are in-different about the alternative interventions.

Obviously, a standard has the least flexibility. Aguideline has significantly more flexibility, and anoption is the most flexible. As noted in the defini-tions, options can exist because of insufficient evi-dence or because patient preferences are divided orunknown. In the following panel recommendations,those regarding treatment choices were labeled op-tions mostly because of insufficient evidence. Noneof the following panel recommendations fits theabove definition of a guideline.

The panel’s recommendations apply to the stan-dard patient, defined as a man who has clinicallylocalized prostate cancer (adenocarcinoma of the

prostate). For this report, the panel focused on clin-ical stage T2 (B) disease. Based on the opinion ofthe panel, recommendations may also be applied topatients diagnosed with stage cT1c disease (detect-ed by elevated PSA). The recommendations werenot developed for patients with stage T1a/b(A1/A2) or clinical T3-T4 (C) disease. For a de-tailed discussion of prostate cancer staging, seepages 13-15.

As a standard, an assessment of the patient’s lifeexpectancy, overall health status and tumor charac-teristics is necessary before any treatment decisionscan be made.

Life expectancy:Life expectancy, rather than pa-tient age, should be the factor considered in treat-ment selection. Therefore, the panel did not set aspecific chronological cutoff point. When a man’slife expectancy is relatively long, prostate cancercan be a cause of morbidity and mortality. On theother hand, at an advanced patient age, or when lifeexpectancy is relatively short, competing hazardsfor mortality reduce the chance that a man will suf-fer from disease progression or die from prostatecancer. (See U.S. Life Expectancy Table in Appen-dix C.)

Health status:The patient’s overall health statusis the sum of all conditions and includes both pa-tient and family history as well as the present stateof the patient’s well-being and the degree of anycoexistent disease. There are two reasons to evalu-ate the overall health status prior to deciding on anintervention: (1) Overall health status influenceslife expectancy; (2) overall health status may affectpatient response to adverse events resulting fromparticular interventions.

Tumor characteristics:The histologic grade andstage of the tumor should be considered when as-sessing the potential natural history and treatmentoptions for prostate cancer. Small, well-differentiat-ed cancers progress more slowly and are less likelyto be life threatening than large, poorly differentiat-

Recommendations: Standards

The standard patient

Chapter 4: Treatment recommendations



ed tumors which have a greater potential to be bio-logically aggressive and clinically significant.

As a standard, a patient with clinically localizedprostate cancer should be informed about the com-monly accepted initial interventions including, at aminimum, radical prostatectomy, radiotherapy andsurveillance. A discussion of the estimates for bene-fits and harms of each intervention should be of-fered to the patient.

The panel defines radical prostatectomy to in-clude complete removal of the prostate, vasalampullae and seminal vesicles. The panel definesradiotherapy to include external beam and/or inter-stitial (brachytherapy) treatments. Surveillance isdefined as periodic monitoring of the patient’s pros-tate cancer and its effects.

The patient should be informed that dependingon his condition and initial choice, subsequent in-terventions may be appropriate.

As a standard, the patient’s preference, based onhis attitude toward the course of the disease and thebenefits and harms of the different interventions,should be considered in determining his treatment.

Options for management of localized prostatecancer include radical prostatectomy, radiotherapyand surveillance. Radiotherapy includes externalbeam and interstitial (brachytherapy) treatments.The panel considers these interventions to be op-tions because data from the literature do not pro-vide clear-cut evidence for the superiority of anyone treatment. Described for each option is the pa-tient most likely to benefit from the intervention.

Radical prostatectomy:Based on the panel’sinterpretation of the literature and panel opinion,the patient most likely to benefit from radical pros-tatectomy would have a relatively long life ex-pectancy, no significant surgical risk factors and apreference to undergo surgery.

Radiotherapy: Based on the panel’s interpreta-tion of the literature and panel opinion, the patientmost likely to benefit from radiotherapy would havea relatively long life expectancy, no significant riskfactors for radiation toxicity and a preference forradiotherapy.

Surveillance: Based on the panel’s interpretationof the literature and panel opinion, patients mostlikely to benefit from surveillance are those with ashorter life expectancy and/or a low-grade tumor.

Radical prostatectomyThe major advantage of radical (total) prostatec-

tomy is its potential for “cure” by removing all ofthe tumor. “Cure” is defined as lifetime freedomfrom disease. Total prostatectomy in the properlyselected patient will provide disease-free survivalrates comparable to the expected survival in simi-larly aged men for up to 30 years of observation(Gibbons, Correa, Brannen, et al., 1989).

The major disadvantage is potential morbidity.Possible operative morbidity includes the follow-ing: bleeding, which can require a transfusion; dif-ficulty with anastomosis of the bladder neck to ure-thra; and rectal injury. These problems will varywith the size and anatomy of the patient’s pelvic or-gans and the experience of the surgeon. Postoperat-ive morbidity includes problems with indwellingcatheters, lymphocele, anastomotic stricture, uri-nary incontinence and impotence (erectile dysfunc-tion).

With regard to impotence, some authors have re-ported postoperative potency rates in the 70-percentrange in patients who were potent preoperatively(Catalona and Bigg, 1990). If impotence occursafter surgery (or radiotherapy or hormone therapy),what is lost is erectile function. The sensation oforgasm may remain intact. In these patients, phar-macologically induced erections (using self-admin-istered penile injections) or use of vacuum constric-tion devices or penile prostheses can provide effect-ive treatment (Lue, Carroll and Moore, 1989).

A number of articles have reported stress urinaryincontinence and/or severe urinary incontinence (re-quiring intervention) following radical prostatec-tomy. The complications summary outcomes table(Table 5) on page 27 shows a reported low of 4 per-cent and a high of 50 percent for stress inconti-nence and a range from 0 percent to 15.4 percentfor severe incontinence. The complications graphfor prostatectomy (Figure 14, page 31) shows howthe reporting series are distributed along these low-high ranges.

For mortality following radical prostatectomy,Table 5 shows a range from 0 percent to 2.1 per-cent. More than half the series reported 0 percent.However, the risk of death from radical prostatec-tomy increases with patient age and was found tobe 1.4 percent in men aged 75 to 80 and 4.6 percent

Advantages and disadvantagesof treatment options

Recommendations:Treatment options



for age 80 and older (Lu-Yao, McLerran, Wasson,et al., 1993).

Pulmonary embolism, in the panel’s review ofthe literature, occurred in 0.8 percent to 7.7 percentof patients after radical prostatectomy. In a reportof Medicare patients (Lu-Yao, McLerran, Wasson,et al., 1993), investigators found cardiopulmonarycomplications in 4 percent of men 65 to 69 years ofage and in 7.4 percent of men 75 to 79 years ofage. Other potential complications, such as anasto-motic stricture, fistula and bowel injuries, occur in-frequently.

Recent developments in the technique of radicalprostatectomy may have reduced the risks of com-plications. Refinements in the understanding of thesurgical anatomy of the prostate have made possi-ble a more meticulous operation, improved opera-tive visualization, reduction in blood loss and im-proved sexual function and urinary continence ratespostoperatively.

Length of hospitalization has also been signifi-cantly reduced in many patients to 3 – 6 days, butthe total cost for radical prostatectomy has not beenwell described and remains a “moving target”(Koch, Smith, Hodge, et al., 1994).

RadiotherapyThe advantage of radiotherapy (external beam

radiotherapy and brachytherapy) is that it not onlyhas a potential for cure, but is well tolerated in themajority of men when modern techniques are used.Its principal potential harms include radiation cysti-tis, proctitis, and erectile dysfunction. Also, becausethe prostate remains in place, persistence and pro-gression of the disease may occur.

External beam radiotherapy

External beam radiotherapy can be an effectivetreatment in the appropriate standard patient afflict-ed with stage T2 prostate cancer. Notwithstandingcaveats regarding survival and disease progressiondata (pages 32-33, 33-34), the results reported inthe literature for external beam radiotherapy appearreasonably favorable. Although some selected se-ries have reported extremely high PSA failures(noted in Hanks, 1994), others have demonstratedextremely favorable PSA control with long-termfollow-up (Hanks, 1994; Hanks, Perez, Kozar, etal., 1993; Pisansky, Cha, Earle, et al., 1993).

However, an accurate characterization of the trueincidence of PSA failure in an unbiased cohort isurgently needed. There is also evidence that clinicallack of local tumor progression may underestimate

the true incidence of cancer remaining in the pros-tate gland. Biopsies of the radiated gland have re-vealed persistent malignancy in at least 30 percentof patients (Kabalin, Hodge, McNeal, et al., 1989;Kaplan, Prestidge, Bagshaw, et al., 1992; Kiesling,McAninch, Goebel, et al., 1980). Recently, TRUS-guided biopsy series in selected patients suggestthat the true incidence of residual cancer may bemuch higher than previously reported.

Regarding toxicity, external beam radiotherapy,as employed in state-of-the-art radiotherapy centers,has the advantage of having become a very well-tolerated treatment. Improvements include higher-energy radiation beams that can be more preciselyfocused, thus sparing larger amounts of normal tis-sue from therapy; improved computer technologythat calculates with greater precision the absorbeddose of radiation and helps optimize treatmentplanning; and more sophisticated planning proce-dures that precisely localize both the tumor volumeand normal tissues, allowing maximal sparing ofnormal tissues and ensuring adequate delivery ofdose to the tumor.

However, there remain many potential complica-tions. The actual incidence of erectile dysfunctionfor patients receiving radiotherapy (as in series ofpatients receiving other forms of therapy) may beunderreported. Diarrhea is a potential problem forthose patients who receive radiation to regionallymphatics. Other potential significant complica-tions include rectal toxicity (proctitis, rectal ulcera-tion, need for colostomy) as well as bladder com-plications (hematuria, cystitis, dysfunctional void-ing).

Brachytherapy

Mature data are only available for the olderretropubic brachytherapy techniques. Althoughproblems have been reported in these mature brach-ytherapy series (page 18), several groups have doc-umented reasonably satisfactory survival results.The 5-year survival data are not yet available forthe newer ultrasound-guided transperineal tech-niques. However, as the outcomes analysis on pages32-33 indicates, the 5-year survival results wouldbe expected to be quite good. In general, eventhough sufficiently mature data are not yet availableto establish superiority of the newer techniques, thepanel knows of no evidence that the results fromthese techniques are inferior to results from the old-er techniques.

One clear advantage of the current brachytherapymethods is patient convenience. Several series ofTRUS-guided transperineal techniques report that



the procedures are usually performed with hospitalstays of 2 days or less. When permanent radionu-clides are implanted, there is usually only a moder-ate amount of postimplantation discomfort, con-trolled in the overwhelming majority of patients byoral pain medications.

Disadvantages of brachytherapy can include in-ferior control of localized tumors. Similar to allprostate cancer treatment modalities, brachytherapyproduces markedly improved local control in low-stage and low- to moderate-grade disease (Carey,Lippert, Constable, et al., 1988; Fuks, Leibel, Wall-ner, et al., 1991; Giles and Brady, 1986; Kuban, El-Mahdi and Schellhammer, 1989a; Morton and Pes-chel, 1988; Smalley and Noble, 1992).

Additionally, the importance of long-term fol-low-up cannot be overemphasized. Several serieshave reported that the mean time to local failure inbrachytherapy-treated patients is in the range of 5to 10 years (Fuks, Leibel, Wallner, et al., 1991;Kuban, El-Mahdi and Schellhammer, 1989a; Small-ey and Noble, 1992). The exceedingly long time tolocal recurrence seen in series that have adequatefollow-up emphasizes both the indolent natural his-tory of the disease and the tentative nature of anyconclusion reached in studies without follow-up of10 to 15 years.

The ability of brachytherapy to control local dis-ease must, therefore, be evaluated on the basis ofseries that have sufficient follow-up. Four differentreports have compared local tumor control withbrachytherapy versus control with alternative thera-pies. Three reported that brachytherapy producedinferior local tumor control when compared witheither external beam radiotherapy or radical prosta-tectomy (Kuban, El-Mahdi and Schellhammer,1989a; Morton and Peschel, 1988; Schellhammer,Whitmore, Kuban, et al., 1989; Smalley and Noble,1992). However, differences in other factors such aspatient selection, rather than the treatment itself,may explain the differences in outcomes.

With regard to complications, those reported inpresent brachytherapy series are remarkably hetero-geneous. They include impotence (erectile dysfunc-tion), with no convincing evidence of less risk thanwith external beam radiotherapy (Smalley andNoble, 1992). For the newer, TRUS-guided trans-perineal techniques, rates for the complications re-ported to date vary widely (Blasko, Ragde andGrimm, 1991; Iversen, Bak, Juul, et al., 1989).

In some stage T2 patients, higher complicationshave been reported for brachytherapy as comparedwith external beam radiotherapy. Also, patients witha previous transurethral resection or significant oth-

er uropathy have a much greater risk of developingsubsequent urinary complications.

SurveillanceOne advantage of surveillance therapy as a treat-

ment option for localized carcinoma of the prostateis its low initial cost. Because most patients can befollowed with DRE and PSA alone, if disease pro-gression does not develop during the patient’s life-time, the cost of such follow-up may be very low.This advantage is dependent upon the assumptionthat most patients will not develop symptomatic ormetastatic disease during their lifetimes. If this as-sumption is incorrect, the cost advantage may dis-appear as it has been estimated that the cost oftreatment for one new case of metastatic prostatecancer is $70,000 (Littrup, Goodman and Mettlin,1993).

Another major advantage of surveillance for lo-calized prostate cancer is its avoidance of morbidityassociated with treatment. Most patients with newlydiagnosed prostate cancer, because of the currentpolicy of early detection and treatment, have nocancer-related symptoms at diagnosis. Surveillancewould allow these men to preserve their quality oflife. Conversely, radiotherapy and radical prostatec-tomy are associated with potential complicationsincluding erectile dysfunction, incontinence and in-jury to various organs from treatment (Fleming,Wasson, Albertsen, et al., 1993).

Finally, survival outcomes for at least 10 yearsare generally good. As summarized on page 19,available data suggest that the risk of metastaticdisease and prostate cancer death in patients man-aged with surveillance alone is not substantiallydifferent from the risk in patients treated for “cure.”A recent pooled analysis of six series of patients sotreated found excellent 10-year disease-specific sur-vivals for patients with well-differentiated andmoderately well-differentiated tumors (Chodak,Thisted, Gerber, et al., 1994). On the other hand,one study reported that the majority of patients onsurveillance who survive more than 10 years ulti-mately die of prostate cancer (Aus, Hugosson andNorlén, 1994).

Among the disadvantages of surveillance is therisk of subsequent, possibly incurable disease. Invirtually every series of patients managed by sur-veillance, some percentage of patients was reportedto have died of the disease and an additional groupwas reported to have suffered from disease-relatedmorbidity. In a pooled analysis, at 10 years of fol-low-up, 6 percent, 6.5 percent and 42 percent ofpatients with well-differentiated, moderately well-



differentiated and poorly differentiated tumors, re-spectively, died of their disease (Chodak, Thisted,Gerber, et al., 1994). Another study reported on 61patients with stages T1-T2 disease managed by sur-veillance. Of 8 who died during the period of ob-servation, 4 died of prostate cancer (Adolfsson andCarstensen, 1991).

Then there is the risk of developing disease-re-lated morbidity. The premise of “curative” treat-ment of carcinoma of the prostate is that it will pre-vent not only cancer-related death, but those com-plications related to the tumor that reduce thepatient’s quality of life. Patients managed with sur-veillance may be at a higher risk for such cancer-re-lated morbidities. Among these complications,spinal cord compression is a major concern. Thisevent can occur in as many as 12 percent of pa-tients with metastatic disease and can lead to deathas well as severe reductions in the patient’s qualityof life (Rubin, Lome and Presman, 1974). Whetherintervention at the time of diagnosis might preventsuch an outcome could not be predicted.

Other disease-related complications include pain,obstructive voiding symptoms, bone fracture ane-mia, ureteral obstruction, uremia, deep venousthrombosis and pulmonary embolism. In one paper,26 of 223 patients followed on a program of sur-veillance developed metastases (Johansson, Adami,Andersson, et al., 1992). Of these 26 patients, 23had a reduction in performance status. Of 19 pa-tients who died of prostate cancer, their perfor-mance status decreased for more than 6 months in12, and 13 patients required hospital care for 1month or more prior to death. Fourteen patients inthis series required hospital care for local problemsdue to their tumors. Of 152 patients who did notdevelop disease progression, 30 had mild or moder-ate local problems and 14 required transurethral re-section of the prostate. Of 71 patients who did de-velop local progression, 60 had local problems(which generally disappeared after treatment withhormone therapy). Twenty-eight of these 71 had re-current local problems during the course of theirdisease.

In summary, using surveillance as the primarymanagement of patients with locally confined pros-tate cancer may place a number of patients at risk

for various complications related to progression ofthe tumor.

As pointed out on page 20, patients who elect topursue a policy of surveillance are free to choose a“curative” intervention at any time during follow-up. However, if the goal for subsequent interventionis to time its application prior to the development ofextraprostatic disease, evidence indicates that thewindow of opportunity is very narrow. Data fromone report suggest that if serum PSA is measuredduring surveillance, once the value exceeds 5 ng/mlthe risk exceeds 50 percent that the disease is ex-traprostatic (Thompson, Zeidman, Crawford, et al.,1993).

Additional treatment may be needed. In virtuallyevery series of patients treated with surveillance forlocalized prostate cancer, the term “surveillance”included a variety of additional forms of treatment.Examples include a series of 122 patients (Adolfs-son, Carstensen and Lowhagen, 1992). Of these, 45percent received endocrine therapy (36 patients),external beam irradiation (12 patients),125I implan-tation (3 patients) or radical prostatectomy (4 pa-tients). In another series, treatment for local pro-gression was required for 23 of 120 patients(George, 1988).

It can be seen then that patients followed withsurveillance may be at risk for deferring treatmentto a later age and, by doing so, either deferring theside effects of treatment or, alternatively, losing theopportunity of disease control as well as undergo-ing invasive therapy at an age when comorbiditiesincrease.

A major unmeasured disadvantage to a policy ofsurveillance is the patient’s possible anxiety, hisfeeling that “nothing is being done about my pros-tate cancer.” Although the patient may intellectuallyunderstand the often confusing data supporting thevalidity of surveillance therapy, considerable anxi-ety can be generated in many patients and theirfamilies by a lack of intervention. The psychologicconsequences of cancer risk or diagnosis awarenessare well recognized, and clinicians practicing in thisfield are well aware of the overpowering dread thatcan be induced by worry about prostate cancer(Lerman, Miller, Scarborough, et al., 1991; Lerman,Rimer and Engstrom, 1991).



The explicit methodology the AUA ProstateCancer Clinical Guidelines Panel used in its analy-sis for this Report on the Management of ClinicallyLocalized Prostate Cancerrequired careful reviewand interpretation of published reports in the peer-reviewed literature. As discussed in Chapter 1,many articles were reviewed and most were reject-ed for a variety of reasons, including inaccurate re-porting of data, limited time of follow-up, incom-plete description of treatments utilized and poorlydefined patient populations. Moreover, the studiesfinally selected for data extraction were not by anymeans free of deficiencies.

Data not based on randomizedcontrolled trials

All the studies finally selected by the panel pro-vided useful information, but most were case seriesnot subjected to the rigors of a carefully performed,prospective, centrally controlled clinical trial. Manyof the patient populations were “convenience sam-ples” selected mainly because they were availablein the clinical settings in which the research wasconducted.

The lack of randomized, controlled trials is aproblem inherent in the medical literature.Although it can be addressed and responded to, itcannot be avoided. Neither can it be dismissed. Thedifficulties this problem creates for developing evi-dence-based practice policy recommendations areespecially severe with regard to localized prostatecancer. Because of the particular attributes of thisdisease, such as high histologic prevalence, yetvariable natural history, treatment outcomes datafrom uncontrolled trials can be even less reliablethan usual.

Insufficient dataMany of the limitations in the literature stem di-

rectly from the previously mentioned plethora of

case series and lack of randomized controlled trials.These limitations include the large gaps that exist inthe literature regarding data reported. For example,many articles do not report all outcomes (such ascancer-specific survival, metastasis-free survivaland tumor-free survival). There are also few data onhigh-grade tumors in patients managed by surveil-lance, or on pelvic lymph node status in patientsmanaged by external beam radiotherapy as well assurveillance. In another very important example,many articles do not specify ages of patients not-withstanding the effect of age on survival and thesignificant differences in average patient age fordifferent treatment modalities. In still another ex-ample, many articles reporting complications fromtreatment do not report “zero complications.” Forinstance, an article may not refer to incontinence inits list of treatment-related complications. Readersare left to wonder whether the complication did notoccur or if it was omitted from the report.

Data variabilityData variability is one of the most frequent limi-

tations encountered when attempting to combineevidence from multiple studies. This variabilitytakes many forms with many causes. Variations be-tween studies because of differences in stagingmethods are one example. Some articles reviewedby the panel reported outcomes according to clini-cal stage, others according to surgical stage. Out-comes data from these two classes of articles arenot comparable.

Lymph node dissections performed for stagingvary between studies. Lymphadenectomy is typical-ly performed, but the panel could not substantiatethat all procedures reported in the literature werecomparable. Both extensive and limited dissectionswere carried out by different surgeons. In addition,although laparoscopic dissections are becomingmore commonplace, they were not included in thearticles selected.

Imaging studies are frequently utilized and arelimited not only by the state-of-the-art technology,but by the abilities of radiologists and urologists tointerpret a particular study. Laboratories vary aswell. Similar studies performed in different facilities,

Limitations in the prostatecancer treatment literature

Chapter 5:Literature limitations and recommendations for research



using different assays, could yield very different re-sults. Urologists and radiologists also differ. It can-not be assumed that a radiation technique or surgicalprocedure performed by one clinician is comparableto that performed by another.

As laboratories and imaging studies vary, so dopathology reports. Controlled trials often utilize acentral pathology facility, but comparing case seriesmeans comparing varied facilities. Differences existin preparation of histologic material, especiallywith the current emphasis on whole mount prostatepreparations. Yet, interpretations of extent of in-volvement and margin status are highly dependenton tissue preparation and subsequent pathologic in-terpretation, which makes comparisions betweenstudies problematic. Similar variations exist in theabilities of pathologists to grade malignancies. Al-though standards have been established, the subjec-tive component of these interpretations cannot beignored.

Patient populations differ as do the methods bywhich patients are selected for review. For instance,some clinical reports include consecutive patients,whereas many others are based upon informal se-lection factors such as availability for follow-up, re-ferral patterns and logistic concerns. Controlledstudies, because of strict inclusion and exclusioncriteria, may be preferable but may not be general-izable because of the carefully selected patients en-rolled. Means and ranges of follow-up often vary aswell. Such variations will not only have an impacton outcomes, but will influence any conclusions de-rived from the studies.

Because selection criteria between studies maydiffer, with variations in patient population, studiesperformed and methods of follow-up, comparisonsof studies may not be reliable. A common problemwith prostate cancer case series, for example, is thereporting of endocrine therapy for patients develop-ing recurrence after surgery or radiotherapy. Thetiming of administration, the form of therapy uti-lized and the method of reporting may not be clear-ly detailed, thus limiting the value of the report.Controlled prospective trials, by contrast, usuallyspecify from the outset the approach to be utilized.

Publication biasPublication bias is a problem affecting the avail-

able data to which there may be no immediate solu-tion. Very simply, because not all physicians pub-lish, case-study results may not be generally repre-

sentative. Moreover, studies with negative or equiv-ocal results are less likely to be submitted for publi-cation and less likely to be published if submitted.

Data limitations in reflectingcurrent techniques

The data available do not always reflect themany changes in treatment modalities that have oc-curred over the past two decades. For instance, ear-ly brachytherapy experience utilizing retropubicimplantation techniques with 131I and 198Au hadhigh failure rates. Newer methods, utilizing differ-ent isotopes (such as iridium) implanted perineallyunder ultrasound guidance, are being used with in-creasing frequency, but too few data are currentlyavailable to make efficacy comparisons.

Similarly, nerve-sparing techniques are being in-creasingly applied to radical prostatectomy. Yet, itmust be assumed that this modification has not hadany impact on survival or progression. In addition,the use of PSA to detect disease recurrence has al-tered the definition of treatment failure. Whetherconcepts regarding success and failure will nowchange because of the availability of this relativelyreliable marker is not known. Many questions re-main: Does PSA failure following radical prostatec-tomy or radiotherapy always indicate treatment fail-ure? What numeric criteria should be used to estab-lish PSA failure? What is its impact on survival?

Finally, new forms of therapy continue to evolve.Cryotherapy and other ablative techniques are beingdeveloped, but too few data are available to appro-priately assess success and failure in order to makemeaningful comparisons with other treatmentmodalities.

Most research needs can be grouped in three cat-egories: (1) new and better methods to diagnoseand manage localized prostate cancer; (2) prospec-tive, randomized, controlled studies of the issuesconcerning prostate cancer, especially controlledstudies of competing treatments for the manage-ment of localized prostate cancer; and (3) studies ofhow prostate cancer and its treatments affect patientquality of life.

Recommendations forfuture research



Needs for new assessment andmanagement methods

Needs for new methods of cancer diagnosis andmonitoring include a more sensitive, more specifictumor indicator. As clinically useful as serum PSAvalues have now become, PSA is not prostate-can-cer specific. As a result, it lacks sufficient sensitivi-ty and specificity to be the ideal screening test forprostate cancer. In addition, although serum PSAconcentration correlates strongly with tumor vol-ume (r = 0.70), it cannot reliably predict tumorstage on an individual basis. Moreover, PSA afterandrogen deprivation therapy may not always be areliable indicator of the true tumor status becausethe cell’s ability to express PSA is under hormonalregulation, and androgen-insensitive cells do notproduce and secrete PSA to the same degree as an-drogen-sensitive cells. Patients with progressivedisease after androgen deprivation therapy may infact have a low or stable serum PSA concentration.

Needed also are biochemical, radiographicand/or genetic methods to reliably determine whichcancers are biologically aggressive and which areclinically insignificant, so that focused treatmentstrategies can be developed such that treatment isinitiated only in those patients with life-threateningprostate tumors.

For detecting potentially life-threatening cancerswhile still localized, it would be useful to have agenetic marker that can identify men likely to de-velop such a tumor in their lifetimes. These mencould then be monitored with appropriate, compre-hensive screening programs. Knowing who is atrisk for developing a clinically significant prostatecancer has tremendous potential not only to in-crease the probability of detecting prostate cancerwhile still organ confined, but to markedly decreasethe health care costs associated with unfocused ef-forts at prostate cancer detection.

Finally, with only 50 to 60 percent of newly di-agnosed prostate cancers currently organ confined,there is an overwhelming need for an effective sys-temic therapy for this disease. At the present time,no curative treatment exists for advanced prostatecancer. None of the currently available chemothera-peutic agents is effective, and androgen deprivationtherapy remains a palliative treatment for most pa-tients. New and creative approaches, such as genetherapy, need to be pursued both at the basic sci-ence level and in prospective clinical trials.

Recommendations for randomizedcontrolled trials

It is clear, from the discussions in this report oflimitations in the prostate cancer treatment litera-ture, that a pressing need exists for properly de-signed and controlled, prospective, randomizedclinical trials to study effectiveness of competingtreatment modalities for localized disease. In partic-ular, randomized, controlled trials are needed tocompare surveillance with the accepted active treat-ments.

Properly designed efficacy studies of treatmentmodalities will provide reliable descriptive data forthe patients studied. The descriptive factors shouldinclude age, tumor stage, tumor grade, ploidy, PSA,performance status and comorbidity, as well as costfactors and validated measures of quality of lifeover the course of a trial. End points measured in atrial should include risk of local recurrence, risk ofdisease progression (including objective measuresof symptoms associated with progression), risk ofmetastatic disease and risk of prostate cancer death.

Following are additional suggested study topicsfor each of the three major modalities:

• Radical prostatectomy: Methods of improv-ing preoperative staging, reducing the numberof patients with extraprostatic disease and re-ducing treatment complications; strategies toreduce the cost of the procedure; better waysto disseminate advances in surgical techniquesto the urologic community; treatments for pa-tients with pathologically proven (pT3) ex-traprostatic disease; and treatments for patientswith evidence of serologic (PSA) failure.

• Radiotherapy: Ways to reduce treatmentmorbidity; ways to standardize treatment; therole of conformal therapy and of radiosensitiz-ers; strategies to reduce the cost of treatment;optimal treatment at progression; mature dataon long-term follow-up of existing radiothera-py patients; stage-specific complications dataon existing series; and PSA and biopsy data.

• Surveillance: Optimal schedule of follow-upand optimal interventions at evidence of pro-gression.

Among the other topics and issues that need tobe addressed in rigorously designed clinical trialsare:

• New technologies for the treatment of clini-cally localized prostate cancer.



• Trade-offs between survival and quality oflife—including analysis of methods by whichpatients make treatment choices and the roleplayed by quality-of-life factors in thosechoices.

• Opportunities for chemoprevention of pros-tate cancer and dietary interventions, hor-monal therapy and retinoid therapy.

• New strategies for the use of hormonal treat-ments.

• Combined therapies for prostate cancer.• Development and validation of surrogate

measures of long-term prostate cancer out-comes (e.g.,validation of PSA failure as asurrogate for cancer survival).

Patient quality of lifeResearch is needed for determining how prostate

cancer and its treatments affect patient quality oflife. Such research would include the second topicin the foregoing list: analysis of trade-offs betweensurvival and quality of life and how quality-of-lifefactors affect patients’ treatment choices. Neededalso are improved methods for enhancing patient

involvement in a meaningful and efficient decision-making process and improved methods for provid-ing unbiased information to patients and physiciansabout emerging processes and outcomes of care.

Further research needsWith the increasing emphasis on efficient alloca-

tion of health care resources, it will be necessary todevelop methods to assess the costs related to treat-ment of prostate cancer. These include the costs ofearly detection, of treatment and of complicationsfrom treatment. It would be useful as well to beable to assess the financial impact of interventionon productive longevity and the costs related to dis-ability, long-term care and management of metasta-tic disease, and to compare these data with similardata regarding the financial impact of the disease it-self.

It would also be helpful for future research tohave a prostate cancer registry established for allprostate cancer cases in the United States. Informa-tion is now available from the Surveillance, Epi-demiology and End Results Program registry, butonly for a limited number of locations around thecountry.Archived Document—

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tion

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log

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1126

Th

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rad

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Ca

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Tabl

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Bib

liogr

aphy

by

Pap

yrus

ref

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umbe

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Page A-5

Pa

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Re

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nce

Jou

rna

lY

ea

rV

olP

ag

es

Titl

eA

utho

rsIn

stitu

tion

2720

Jour

nal o

f U

rolo

gy19

8012

485

5-85

9D

efin

itive

ra

dia

tion

th

era

py

for

pro

sta

ticca

rcin

om

a:

Ma

yo c

linic

exp

eri

en

ceC

up

ps,

R.E

., U

tz,

D.C

., F

lem

ing

, T

.R.,

Ca

rso

n,

C.C

., Z

inck

e,

H.,

an

d M

yers

, R

.P.

Ma

yo C

linic

an

d M

ayo

Fo

un

da

tion

2729

Jour

nal o

f U

rolo

gy19

8112

536

5-36

9T

ran

sco

ccyg

ea

l 1

25

iod

ine

pro

sta

tic i

mp

lan

tatio

nfo

r a

de

no

carc

ino

ma

Am

bro

se,

S.S

.E

mo

ry U

niv

ers

ity S

cho

ol

of

Me

dic

ine

2783

Uro

log

ic C

linic

s o

f N

ort

hA

me

rica

1980

762

3-62

9T

he

th

era

pe

utic

ro

le o

f p

elv

ic l

ymp

ha

de

ne

cto

my

in p

rost

atic

ca

nce

rM

ora

les,

P.,

Go

limb

u,

M.

Ne

w Y

ork

Un

ive

rsity

Me

dic

al

Ce

nte

r

2806

Uro

logy

1981

1739

-43

Lym

ph

oce

le a

fte

r p

elv

ic l

ymp

ha

de

ne

cto

my

for

uro

log

ic c

an

cer

So

ga

ni,

P.C

., W

ats

on

, R

.C.,

an

dW

hitm

ore

, W

.F.,

Jr.

Me

mo

ria

l S

loa

n-K

ett

eri

ng

Ca

nce

r C

en

ter

2894

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1979

519

57-

1961

Pre

op

era

tive

ext

en

de

d f

ield

ra

dia

tion

with

I-1

25

see

d i

mp

lan

t in

pro

sta

tic c

an

cer:

a p

relim

ina

ryre

po

rt o

f a

ra

nd

om

ize

d s

tud

y

Ch

ary

ulu

, K

., B

lock

, N

., a

nd

Su

da

rsa

na

m,

A.

Un

ive

rsity

of

Mia

mi

Sch

oo

l o

f M

ed

icin

e

3019

Uro

logy

1979

1455

5-56

0R

ad

iatio

n t

he

rap

y a

s d

efin

itive

tre

atm

en

t fo

rlo

caliz

ed

ca

rcin

om

a o

f p

rost

ate

Jazy

, F

.K.,

Aro

n,

B.,

De

ttm

er,

C.M

., a

nd

Sh

eh

ata

, W

.M.

Un

ive

rsity

of

Cin

cin

na

ti M

ed

ica

l C

en

ter

(mu

lti-s

ite)

3050

Ca

nce

r19

7943

1123

-11

27R

ad

iatio

n t

he

rap

y fo

r lo

caliz

ed

pro

sta

te c

an

cerT

ayl

or,

W.J

., R

ich

ard

son

, R

.G.,

an

dH

afer

man

n, M

.D.

Vir

gin

ia M

aso

n M

ed

ica

l C

en

ter

3087

Jour

nal o

f U

rolo

gy19

7912

144

7-45

1C

om

plic

atio

ns

of

12

5io

din

e i

mp

lan

tatio

n a

nd

pe

lvic

lym

ph

ad

en

ect

om

y in

th

e t

rea

tme

nt

of

pro

sta

tic c

an

cer

Fo

wle

r, J

.E.,

Jr.

, B

arz

ell,

W.,

Hila

ris,

B.S

., a

nd

Wh

itmo

re,

W.F

., J

r.M

em

ori

al

Slo

an

-Ke

tte

rin

g C

an

cer

Ce

nte

r

3195

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1980

611

21-

1126

Th

e a

dve

rse

in

flue

nce

of

pri

or

tra

nsu

reth

ral

rese

ctio

n o

n p

rog

no

sis

in c

arc

ino

ma

of

pro

sta

tetr

ea

ted

by

rad

iatio

n t

he

rap

y

McG

owan

, D.G

.C

ross

Ca

nce

r In

stitu

te (

mu

lti-s

ite)

3399

Ca

nce

r19

8045

1906

-19

11R

ad

ica

l su

rge

ry f

or

pro

sta

tic c

an

cer

Wa

lsh

, P

.C.,

Je

we

tt,

H.J

.T

he

Jo

hn

s H

op

kin

s U

niv

ers

ity a

nd

Ho

spita

l34

01C

an

cer

1980

4519

22-

1928

Co

mb

ine

d i

nte

rstit

ial

an

d e

xte

rna

l ra

dio

the

rap

y in

the

de

finiti

ve m

an

ag

em

en

t o

f ca

rcin

om

a o

f th

ep

rost

ate

Gu

err

iero

, W

.G.,

Ca

rlto

n,

C.E

., J

r.,

an

dH

udgi

ns, P

.T.

Ba

ylo

r C

olle

ge

of

Me

dic

ine

(m

ulti

-site

)

3480

Jour

nal o

f U

rolo

gy19

8012

449

5-49

7R

ad

ica

l re

tro

pu

bic

pro

sta

tect

om

y a

fte

rtr

an

sure

thra

l p

rost

atic

re

sect

ion

Ba

ss,

R.B

., J

r.,

Ba

rre

tt,

D.M

.M

ayo

Clin

ic a

nd

Ma

yo F

ou

nd

atio

n

3649

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1981

788

5-89

0R

ad

ica

l e

xte

rna

l ra

dio

the

rap

y fo

r p

rost

atic

carc

ino

ma

Be

iler,

D.D

., W

rig

ht,

D.J

., a

nd

Re

dd

y,G

.N.

Ge

isin

ge

r M

ed

ica

l C

en

ter

3789

Uro

logy

1981

177-

11V

AC

UR

G r

an

do

miz

ed

tri

al

of

rad

ica

lp

rost

ate

cto

my

for

sta

ge

s I

an

d I

I p

rost

ate

ca

nce

r.V

ete

ran

s A

dm

inis

tra

tion

Co

op

era

tive

Uro

log

ica

lR

ese

arc

h G

rou

p

Bya

r, D

.P.,

Co

rle

, D

.K.

Clin

ica

l D

iag

no

stic

Tri

als

Se

ctio

n,

Na

tion

al

Ca

nce

r In

stitu

te

3868

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1981

781

7-81

9P

rop

hyl

act

ic p

elv

ic g

ird

le i

rra

dia

tion

in

th

etr

ea

tme

nt

of

pro

sta

tic c

arc

ino

ma

Ha

zra

, T

.A.,

Gir

i, S

.V

irg

inia

Co

mm

on

we

alth

Un

ive

rsity

(m

ulti

-si

te)

3898

Jour

nal o

f U

rolo

gy19

8112

636

6-37

1In

ters

titia

l ir

rad

iatio

n o

f ca

rcin

om

a o

f th

e p

rost

ate

with

12

5io

din

e a

nd

sim

ulta

ne

ou

s e

xtra

pe

rito

ne

al

pe

lvic

lym

ph

ad

en

ect

om

y in

32

pa

tien

ts:

tria

ls,

trib

ula

tion

s a

nd

po

ssib

le t

riu

mp

hs

Wh

iteh

ea

d,

E.D

., H

uh

, S

.H.,

Ga

rcia

, R

.L.,

Ra

o,

R.,

an

d L

eite

r, E

.B

eth

Isr

ae

l M

ed

ica

l C

en

ter

3914

Th

e J

ou

rna

l o

f th

e K

an

sas

Me

dic

al

So

cie

ty19

8182

278-

281

Pro

sta

tic c

arc

ino

ma

. T

rea

tme

nt

with

I1

25

inte

rstit

ial

irra

dia

tion

an

d p

elv

icly

mp

ha

de

ne

cto

my

Me

bu

st,

W.K

., W

eig

el,

J.W

., a

nd

Re

dd

y,E

.K.

Th

e U

niv

ers

ity o

f K

an

sas

Sch

oo

l o

fM

ed

icin

e

4076

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1982

819

09-

1914

Lo

cal

con

tro

l a

nd

su

rviv

al

aft

er

ext

ern

al

irra

dia

tion

fo

r a

de

no

carc

ino

ma

of

the

pro

sta

teR

an

ga

la,

N.,

Co

x, J

.D.,

Byh

ard

t, R

.W.,

Wils

on

, J.

F.,

Gre

en

be

rg,

M.,

an

d L

op

es

da

Co

nce

ica

o,

A.

Th

e M

ed

ica

l C

olle

ge

of

Wis

con

sin

(m

ulti

-si

te)

4106

Jour

nal o

f U

rolo

gy19

8212

850

2-50

4R

ad

ica

l su

rge

ry v

ers

us

rad

ioth

era

py

for

ad

en

oca

rcin

om

a o

f th

e p

rost

ate

Pa

uls

on

, D

.F.,

Lin

, G

.H.,

Hin

sha

w,

W.,

Ste

ph

an

i, S

., a

nd

Th

e U

ro-O

nco

log

yR

ese

arc

h G

rou

p

Du

ke U

niv

ers

ity M

ed

ica

l C

en

ter

4110

Jour

nal o

f U

rolo

gy19

8212

850

5-50

9R

ad

ioth

era

py

for

pro

sta

tic c

arc

ino

ma

: p

ost

-ir

rad

iatio

n p

rost

atic

bio

psy

an

d r

ecu

rre

nce

pa

tte

rns

with

lon

g-t

erm

fo

llow

up

Le

ach

, G

.E.,

Co

op

er,

J.F

., K

ag

an

, A

.R.,

Sn

yde

r, R

., a

nd

Fo

rsyt

he

, A

.K

ais

er

Fo

un

da

tion

Ho

spita

l (m

ulti

-site

)


Page A-6

4208

Uro

logy

1982

2059

1-59

81

25

I im

pla

nta

tion

fo

r ca

rcin

om

a o

f p

rost

ate

.F

urt

he

r fo

llow

-up

of

first

10

0 c

ase

sG

ross

ma

n,

H.B

., B

ata

ta,

M.,

Hila

ris,

B.,

an

d W

hitm

ore

, W

.F.,

Jr.

Me

mo

ria

l S

loa

n-K

ett

eri

ng

Ca

nce

r C

en

ter

4280

Jour

nal o

f U

rolo

gy19

8212

792

3-92

7C

linic

al

resu

lts o

f e

arl

y st

ag

e p

rost

atic

ca

nce

rtr

ea

ted

by

pe

lvic

lym

ph

ad

en

ect

om

y a

nd

12

5io

din

eim

pla

nts

Ka

nd

zari

, S

.J.,

Be

lis,

J.A

., K

im,

J.C

.,G

ne

pp

, D

.R.,

an

d R

iley,

R.S

.W

est

Vir

gin

ia U

niv

ers

ity M

ed

ica

l C

en

ter

4285

Jour

nal o

f U

rolo

gy19

8212

770

4-70

6R

ad

ica

l p

eri

ne

al

pro

sta

tect

om

y fo

r cl

inic

al

sta

ge

B2

ca

rcin

om

a o

f th

e p

rost

ate

Eld

er,

J.S

., J

ew

ett

, H

.J.,

an

d W

als

h,

P.C

.Th

e J

oh

ns

Ho

pki

ns

Un

ive

rsity

an

dH

osp

ital

4287

Jour

nal o

f U

rolo

gy19

8212

769

9-70

1P

relim

ina

ry o

bse

rva

tion

s o

n t

he

re

sults

of

com

bin

ed

12

5io

din

e s

ee

d i

mp

lan

tatio

n a

nd

ext

ern

al

irra

dia

tion

fo

r ca

rcin

om

a o

f th

e p

rost

ateR

oss

, G

., J

r.,

Bo

rko

n,

W.D

., L

an

dry

, L

.J.,

Ed

wa

rds,

F.M

., W

ein

ste

in,

S.H

., a

nd

Ab

ad

ir,

R.

Un

ive

rsity

of

Mis

sou

ri S

cho

ol o

fM

ed

icin

e

4345

Uro

logy

1982

1937

-42

Cry

osu

rge

ry i

n p

rost

atic

ca

nce

r: s

urv

iva

lB

on

ne

y, W

.W.,

Fa

llon

, B

., G

erb

er,

W.L

.,H

aw

tre

y, C

.E.,

Lo

en

ing

, S

.A.,

Na

raya

na

,A

.S.,

Pla

tz,

C.E

., R

ose

E.F

., S

all,

J.C

.,S

chm

idt,

J.D

., a

nd

Cu

lp,

D.A

.

Un

ive

rsity

of

Iow

a (

mu

lti-s

ite)

4383

Au

stra

lian

& N

ew

Ze

ala

nd

Jour

nal o

f S

urge

ry19

8353

561-

565

Ra

dic

al

rad

ioth

era

py

for

carc

ino

ma

of

the

pro

sta

te:

loca

lize

d a

nd

ext

en

de

d f

ield

tre

atm

en

tNa

cey,

J.N

.D

un

ed

in H

osp

ital

4401

Ca

nce

r19

8351

1599

-16

04P

roto

ns

or

me

ga

volta

ge

X-r

ays

as

bo

ost

th

era

py

for

pa

tien

ts i

rra

dia

ted

fo

r lo

caliz

ed

pro

sta

ticca

rcin

om

a.

An

ea

rly

ph

ase

I/I

I co

mp

ari

son

Du

tte

nh

ave

r, J

.R.,

Sh

iple

y, W

.U.,

Pe

rro

ne

,T

., V

erh

ey,

L.J

., G

oite

in,

M.,

Mu

nze

nri

de

r, J

.E.,

Pro

ut,

G.R

., P

ark

hu

rst,

E.C

., a

nd

Su

it, H

.D.

Ma

ssa

chu

sett

s G

en

era

l H

osp

ital

(mu

lti-

site

)

4639

Th

e C

an

ad

ian

Jo

urn

al

of

Sur

gery

1983

2636

3-36

5In

ters

titia

l ra

dio

the

rap

y fo

r lo

caliz

ed

ca

rcin

om

a o

fth

e p

rost

ate

Wils

on

, J.

W.L

., M

ora

les,

A.,

Bru

ce,

A.W

.,a

nd

Fro

ud

, P

.Q

ue

en

's U

niv

ers

ity

4897

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1984

1018

61-

1867

Tre

atm

en

t-re

late

d m

orb

idity

in

ph

ase

III

RT

OG

stu

die

s o

f e

xte

nd

ed

-fie

ld i

rra

dia

tion

fo

r ca

rcin

om

ao

f th

e p

rost

ate

Pile

pic

h,

M.V

., K

rall,

J.,

Ge

org

e,

F.W

.,A

sbe

ll, S

.O.,

Ple

nk,

H.D

., J

oh

nso

n,

R.J

.,S

tetz

, J.

, Z

inn

ing

er,

M.,

an

d W

alz

, B

.J.W

ash

ing

ton

Un

ive

rsity

Sch

oo

l o

fM

ed

icin

e (

mu

lti-s

ite)

4922

Jou

rna

l o

f th

e M

issi

ssip

pi

Sta

teM

ed

ica

l A

sso

cia

tion

1984

2532

4-32

7E

xte

rna

l b

ea

m i

rra

dia

tion

fo

r p

rost

ate

ca

nce

r: t

he

MB

MC

exp

eri

en

ce a

nd

a l

itera

ture

re

vie

wR

ea

ga

n,

M.T

., S

mith

, R

.A.,

an

dS

tea

dh

am

, R

.E.

Mis

siss

ipp

i B

ap

tist

Me

dic

al

Ce

nte

r

5077

Ca

nce

r19

8453

1857

-18

63R

ela

tion

ship

of

pre

tre

atm

en

t tr

an

sure

thra

lre

sect

ion

of

the

pro

sta

te t

o s

urv

iva

l w

itho

ut

dis

tan

tm

eta

sta

ses

in p

atie

nts

tre

ate

d w

ith 1

25

I-im

pla

nta

tion

fo

r lo

caliz

ed

pro

sta

tic c

an

cer

Fo

wle

r, J

.E.,

Jr.

, F

ish

er,

H.A

.G.,

Ka

ise

r,D

.L.,

an

d W

hitm

ore

, W

.F.,

Jr.

Me

mo

ria

l S

loa

n-K

ett

eri

ng

Ca

nce

rIn

stitu

te

52

05

Th

e P

rost

ate

19

84

519

-25

Ca

rcin

om

a o

f th

e p

rost

ate

: re

sults

of

po

st-

irra

dia

tion

bio

psy

Fre

iha

, F

.S.,

Ba

gsh

aw

, M

.A.

Sta

nfo

rd U

niv

ers

ity S

cho

ol

of

Me

dic

ine

52

19

Ra

dio

the

rap

y a

nd

On

colo

gy

19

84

130

9-31

5E

xte

rna

l b

ea

m r

ad

ioth

era

py

in c

an

cer

of

the

pro

sta

te.

Th

e U

niv

ers

ity o

f A

rizo

na

exp

eri

en

ceA

rist

iza

ba

l, S

.A.,

Ste

inb

ron

n,

D.,

an

dH

eu

sin

kve

ld,

R.S

.U

niv

ers

ity o

f A

rizo

na

He

alth

Sci

en

ces

Ce

nte

r52

65C

an

cer

1984

5337

-43

Ext

ern

al

be

am

irr

ad

iatio

n o

f p

rost

ate

ca

nce

r.E

xpe

rie

nce

in

16

3 p

atie

nts

Ku

rup

, P

., K

ram

er,

T.S

., L

ee

, M

.S.,

an

dP

hill

ips,

R.

Ru

sh-P

resb

yte

ria

n-S

t. L

uke

's M

ed

ica

lC

en

ter

(mu

lti-s

ite)

5610

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1985

1117

77-

1781

Iod

ine

-12

5 i

mp

lan

ts f

or

carc

ino

ma

of

the

pro

sta

tePe

sch

el,

R.E

., F

og

el,

T.D

., K

aci

nsk

i,B

.M.,

Ke

lly,

K.,

an

d M

ate

, T

.P.

Ya

le U

niv

ers

ity S

cho

ol

of

Me

dic

ine

5631

Jour

nal o

f U

rolo

gy19

8513

411

49-

1151

Ne

rve

-sp

ari

ng

ra

dic

al

pro

sta

tect

om

y:e

xtra

pro

sta

tic t

um

or

ext

en

sio

n a

nd

pre

serv

atio

n o

fe

rect

ile f

un

ctio

n

Ca

talo

na

, W

.J.,

Dre

sne

r, S

.M.

Wa

shin

gto

n U

niv

ers

ity S

cho

ol

of

Me

dic

ine

5642

Jour

nal o

f U

rolo

gy19

8513

411

40-

1145

12

5Io

din

e i

mp

lan

tatio

n f

or

carc

ino

ma

of

the

pro

sta

te:

5-y

ea

r su

rviv

al

fre

e o

f d

ise

ase

an

din

cid

en

ce o

f lo

cal

failu

re

Sch

ellh

am

me

r, P

.F.,

El-

Ma

hd

i, A

.E.,

La

da

ga

, L

.E.,

an

d S

chu

lthe

iss,

T.

Ea

ste

rn V

irg

inia

Me

dic

al

Sch

oo

l

5732

Uro

logy

1985

261-

3R

ad

ica

l p

rost

ate

cto

my

for

sta

ge

A2

an

d B

pro

sta

tic c

arc

ino

ma

. O

pe

rativ

e e

xpe

rie

nce

Fo

wle

r, J

.E.,

Jr.

Un

ive

rsity

of

Vir

gin

ia S

cho

ol

of

Me

dic

ine

5813

Uro

logy

1985

2522

8-23

2P

rost

ate

ca

nce

r: e

xpe

rie

nce

with

de

finiti

veir

rad

iatio

n i

n t

he

ag

ed

Gre

en

, N

., B

od

ne

r, H

., a

nd

Bro

th,

E.

LA

C/U

SC

Me

dic

al

Ce

nte

r (m

ulti

-site

)

6141

Clin

ica

l R

ad

iolo

gy

1986

3747

3-47

7R

ad

ica

l tr

ea

tme

nt

of

pro

sta

tic c

arc

ino

ma

by

me

ga

volta

ge

X-r

ay

the

rap

yP

rest

on

, C

.I.,

Du

nca

n,

W.,

an

d K

err

, G

.R.

We

ste

rn G

en

era

l H

osp

ital

6163

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1986

1217

21-

1727

Cu

rre

nt

con

flict

s in

th

e m

an

ag

em

en

t o

f p

rost

atic

can

cer

Ba

gsh

aw

, M

.A.

Sta

nfo

rd U

niv

ers

ity S

cho

ol

of

Me

dic

ine


Page A-7

Pa

pyr

us

Re

fere

nce

Jou

rna

lY

ea

rV

olP

ag

es

Titl

eA

utho

rsIn

stitu

tion

6191

Jour

nal o

f U

rolo

gy19

8613

642

2-42

4P

atie

nt

surv

iva

l a

nd

lo

cal

recu

rre

nce

ra

tefo

llow

ing

ra

dic

al

pro

sta

tect

om

y fo

r p

rost

atic

carc

ino

ma

Mid

dle

ton

, R

.G.,

Sm

ith,

J.A

., J

r.,

Me

lze

r,R

.B.,

an

d H

am

ilto

n,

P.E

.U

niv

ers

ity o

f U

tah

Sch

oo

l o

f M

ed

icin

e

6215

Th

e M

ed

ica

l Jo

urn

al

of

Au

stra

lia19

8614

462

4-62

8H

igh

-do

se r

ad

ioth

era

py

for

loca

lize

d p

rost

atic

can

cer.

An

an

aly

sis

of

tre

atm

en

t re

sults

an

d e

arl

yco

mp

lica

tion

s

Ke

ars

ley,

J.H

.Q

ue

en

sla

nd

Ra

diu

m I

nst

itute

(m

ulti

-site

)

6331

Jour

nal o

f U

rolo

gy19

8613

551

7-51

9P

rost

atic

ca

rcin

om

a:

5-y

ea

r fo

llow

up

of

pa

tien

tsw

ith s

urg

ica

lly s

tag

ed

dis

ea

se u

nd

erg

oin

ge

xte

nd

ed

fie

ld r

ad

iatio

n

Sa

use

, W

.T.,

Ric

ha

rds,

R.S

., a

nd

Ple

nk,

H.P

.L

DS

Ho

spita

l (m

ulti

-site

)

6344

Jour

nal o

f U

rolo

gy19

8613

572

2-72

5P

relim

ina

ry o

bse

rva

tion

s o

n t

he

re

sults

of

com

bin

ed

te

mp

ora

ry 1

92

irid

ium

im

pla

nta

tion

an

de

xte

rna

l b

ea

m i

rra

dia

tion

fo

r ca

rcin

om

a o

f th

ep

rost

ate

Bo

sch

, P

.C.,

Fo

rbe

s, K

.A.,

Pra

ssvi

nic

ha

i,S

., M

ille

r, J

.B.,

Go

lji,

H.,

an

d M

art

in,

D.C

.

Lo

ng

Be

ach

Ve

tera

ns

Ad

min

istr

atio

nM

ed

ica

l C

en

ter

(mu

lti-s

ite)

6364

Uro

logy

1986

2710

-16

Co

mp

ari

son

of

wh

ole

pe

lvis

ve

rsu

s sm

all-

field

rad

iatio

n t

he

rap

y fo

r ca

rcin

om

a o

f p

rost

ate

Plo

yso

ng

san

g,

S.,

Aro

n,

B.S

., S

he

ha

ta,

W.M

., J

azy

, F

.K.,

Sco

tt,

R.M

., H

o,

P.Y

.,a

nd

Mo

ran

d,

T.M

.

Ch

rist

Ho

spita

l (m

ulti

-site

)

6601

Uro

log

ic C

linic

s o

f N

ort

hA

me

rica

1987

1467

5-68

4R

ad

ioth

era

py

vers

us

surg

ery

fo

r lo

caliz

ed

pro

sta

ticca

nce

rP

au

lso

n,

D.F

.D

uke

Un

ive

rsity

Me

dic

al

Ce

nte

r

6732

Pro

gre

ss i

n C

linic

al

&B

iolo

gic

al

Re

sea

rch

1987

243B

379-

386

Ra

dio

the

rap

y o

f st

ag

e B

2 l

esi

on

s o

f th

e p

rost

ateB

ag

sha

w,

M.A

.S

tan

ford

Un

ive

rsity

Sch

oo

l o

f M

ed

icin

e

6813

Ra

dio

the

rap

y a

nd

On

colo

gy

1987

107-

15R

ad

ioth

era

py

of

pro

sta

te c

arc

ino

ma

: re

sults

of

tre

atm

en

t a

nd

co

mp

lica

tion

sS

ack

, H

., N

osb

ue

sch

, H

., a

nd

Stu

etz

er,

H.

Un

ive

rsity

of

Co

log

ne

6860

An

tica

nce

r R

ese

arc

h19

877

395-

399

Pre

tre

atm

en

t tr

an

sure

thra

l re

sect

ion

of

pro

sta

teca

nce

r a

nd

dis

ea

se-f

ree

su

rviv

al

Na

tara

jan

, N

., M

ett

lin,

C.,

Mu

rph

y, G

.P.,

an

d S

chm

idt,

J.

Ro

swe

ll P

ark

Me

mo

ria

l In

stitu

te (

mu

lti-

site

)69

35In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1987

1349

9-50

5A

te

n y

ea

r fo

llow

-up

of

68

2 p

atie

nts

tre

ate

d f

or

pro

sta

te c

an

cer

with

ra

dia

tion

th

era

py

in t

he

Un

ited

Sta

tes

Ha

nks

, G

.E.,

Dia

mo

nd

, J.

J.,

Kra

ll, J

.M.,

Ma

rtz,

K.L

., a

nd

Kra

me

r, S

.U

niv

ers

ity o

f P

en

nsy

lva

nia

/Fo

x C

ha

seC

an

cer

Ce

nte

r (m

ulti

-site

)

6937

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1987

1310

13-

1020

Pro

sta

tic c

arc

ino

ma

: lim

ited

fie

ld i

rra

dia

tion

Ro

un

savi

lle,

M.C

., G

ree

n,

J.P

., V

ae

th,

J.M

., P

urd

on

, R

.P.,

an

d H

eltz

el,

M.M

.C

hild

ren

's H

osp

ital

(mu

lti-s

ite)

7164

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1988

1513

07-

1316

Ele

ctiv

e p

elv

ic i

rra

dia

tion

in

sta

ge

A2

, B

carc

ino

ma

of

the

pro

sta

te:

an

aly

sis

of

RT

OG

77

06

Asb

ell,

S.O

., K

rall,

J.M

., P

ilep

ich

, M

.V.,

Ba

erw

ald

, H

., S

au

se,

W.T

., H

an

ks,

G.E

.,a

nd

Pe

rez,

C.A

.

Alb

ert

Ein

ste

in M

ed

ica

l C

en

ter

(mu

lti-

site

)

7419

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1988

1513

17-

1322

Ad

en

oca

rcin

om

a o

f th

e p

rost

ate

: ra

dio

act

ive

go

ldse

ed

im

pla

nt

plu

s e

xte

rna

l ir

rad

iatio

nG

utie

rre

z, A

.E.,

Me

rin

o,

O.R

.R

ad

iatio

n O

nco

log

y S

ect

ion

, S

t. J

ose

ph

Ho

spita

l

7519

Sca

nd

ina

via

n J

ou

rna

l o

fU

rolo

gy &

Nep

hrol

ogy

-S

up

ple

me

ntu

m

1988

110

95-1

00T

rea

tme

nt

of

loca

lize

d p

rost

atic

ca

nce

r. R

ad

ica

lp

rost

ate

cto

my

vers

us

pla

ceb

o.

A 1

5-y

ea

r fo

llow

-up

Ma

dse

n,

P.O

., G

rave

rse

n,

P.H

., G

ass

er,

T.C

., a

nd

Co

rle

, D

.K.

Will

iam

S.

Mid

dle

ton

Me

mo

ria

l V

ete

ran

sH

osp

ital

(mu

lti-s

ite)

7522

Sca

nd

ina

via

n J

ou

rna

l o

fU

rolo

gy &

Nep

hrol

ogy

-S

up

ple

me

ntu

m

1988

110

89-9

4R

ad

iatio

n t

he

rap

y fo

r p

rost

atic

ca

rcin

om

aB

erg

ma

n,

B.,

Mo

dig

, H

.D

ep

art

me

nts

of

Uro

log

y &

An

dro

log

y a

nd

On

colo

gy,

Un

vers

ity o

f U

me

a

7644

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1988

1411

53-

1157

Iod

ine

-12

5 i

mp

lan

ts v

ers

us

ext

ern

al

be

am

th

era

py

for

sta

ge

s A

2,

B,

an

d C

pro

sta

te c

an

cer

Mo

rto

n,

J.D

., P

esc

he

l, R

.E.

Ya

le U

niv

ers

ity S

cho

ol

of

Me

dic

ine

7670

Jour

nal o

f U

rolo

gy19

8813

998

5-98

8In

ters

titia

l g

old

an

d e

xte

rna

l b

ea

m i

rra

dia

tion

fo

rp

rost

ate

ca

nce

rB

oile

au

, M

.A.,

Do

wlin

g,

R.A

., G

on

zale

s,M

., H

an

de

l, P

.H.,

Be

nso

n,

G.S

., a

nd

Co

rrie

re,

J.N

., J

r.

Un

ive

rsity

of

Te

xas

Me

dic

al

Sch

oo

l

7671

Jour

nal o

f U

rolo

gy19

8813

998

9-99

4C

om

bin

ed

go

ld s

ee

d i

mp

lan

tatio

n a

nd

ext

ern

al

rad

ioth

era

py

for

sta

ge

B2

or

C p

rost

ate

ca

nce

rCa

rey,

P.O

., L

ipp

ert

, M

.C.,

Co

nst

ab

le,

W.C

., J

on

es,

D.,

an

d T

alto

n,

B.M

.U

niv

ers

ity o

f V

irg

inia

Me

dic

al

Sch

oo

l(m

ulti

-site

)77

65A

me

rica

n J

ou

rna

l o

f C

linic

al

On

colo

gy

1988

1116

6-17

1R

ad

iatio

n-t

rea

ted

ca

rcin

om

a o

f p

rost

ate

.C

om

pa

riso

n o

f su

rviv

al

of

bla

ck a

nd

wh

itep

atie

nts

by

Gle

aso

n's

gra

din

g s

yste

m

Azi

z, H

., R

otm

an

, M

., T

he

lmo

, W

., C

he

n,

P.,

Ch

oi,

K.N

., K

hil,

S.U

., L

au

ng

an

i, G

.B.,

Bra

nd

ys,

M.,

Ayr

, G

., a

nd

Ma

cch

ia,

R.J

.Sta

te U

niv

ers

ity o

f N

ew

Yo

rk-H

ea

lthS

cie

nce

Ce

nte

r a

t B

roo

klyn


Page A-8

7796

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1988

1470

1-70

9T

he

ro

le o

f ra

dia

tion

th

era

py

in s

tag

es

A2

an

d B

ad

en

oca

rcin

om

a o

f th

e p

rost

ate

Za

ga

rs,

G.K

., v

on

Esc

he

nb

ach

, A

.C.,

Joh

nso

n,

D.E

., a

nd

Osw

ald

, M

.J.

Th

e U

niv

ers

ity o

f T

exa

s M

.D.

An

de

rso

nH

osp

ital

(mu

lti-s

ite)

7832

Uro

logy

1988

3119

1-19

7R

ad

ica

l p

rost

ate

cto

my.

Pa

tte

rns

of

loca

l fa

ilure

an

d s

urv

iva

l in

67

pa

tien

tsS

che

llha

mm

er,

P.F

.E

ast

ern

Vir

gin

ia M

ed

ica

l S

cho

ol

8161

Inte

rna

tion

al

Uro

log

y &

Nep

hrol

ogy

1989

2132

5-33

2E

xpe

rie

nce

in

th

e t

rea

tme

nt

of

loca

lize

dca

rcin

om

a o

f th

e p

rost

ate

by

de

finiti

ve e

xte

rna

lir

rad

iatio

n

Ku

ten

, A

., N

itetz

ky,

S.,

Ta

tch

er,

M.,

Co

he

n,

Y.,

an

d R

ob

inso

n,

E.

Te

chn

ion

-Isr

ae

l In

stitu

te o

f T

ech

no

log

y(m

ulti

-site

)

8182

Jour

nal o

f U

rolo

gy19

8914

212

62-

1265

Pa

tte

rn o

f fa

ilure

aft

er

rad

ica

l re

tro

pu

bic

pro

sta

tect

om

y fo

r cl

inic

ally

an

d p

ath

olo

gic

ally

loca

lize

d a

de

no

carc

ino

ma

of

the

pro

sta

te:

influ

en

ce o

f tu

mo

r d

eo

xyri

bo

nu

cle

ic a

cid

plo

idy

Blu

te,

M.L

., N

ativ

, O

., Z

inck

e,

H.,

Fa

rro

w,

G.M

., T

he

rne

au

, T

., a

nd

Lie

be

r,M

.M.

Ma

yo C

linic

82

57

Ra

dio

the

rap

y a

nd

On

colo

gy

19

89

16

1-21

Fa

cto

rs i

nflu

en

cin

g o

utc

om

e o

f d

efin

itive

rad

ioth

era

py

for

loca

lize

d c

arc

ino

ma

of

the

pro

sta

te

Pe

rez,

C.A

., G

arc

ia,

D.,

Sim

pso

n,

J.R

.,Z

ivn

usk

a,

F.,

an

d L

ock

ett

, M

.A.

Ma

llin

ckro

dt

Inst

itute

of

Ra

dio

log

y (m

ulti

-si

te)

8280

Uro

logy

1989

3317

-20

Pa

tien

t se

lect

ion

fo

r ra

dic

al

pro

sta

tect

om

yS

mith

, J.

A.,

Jr.

Un

ive

rsity

of

Uta

h C

en

ter

for

He

alth

Sci

en

ces

83

18

Bri

tish

Jo

urn

al o

f U

rolo

gy

19

89

63

191-

195

Re

tro

spe

ctiv

e s

tud

y o

f ra

dio

the

rap

y in

ea

rly

carc

ino

ma

of

the

pro

sta

teR

ea

d,

G.,

Po

into

n,

R.C

.S.

Ch

rist

ie H

osp

ital

(mu

lti-s

ite)

8331

Ca

nce

r19

8963

2468

-24

74E

xte

rna

l b

ea

m r

ad

ioth

era

py

for

carc

ino

ma

of

the

pro

sta

teS

ag

erm

an

, R

.H.,

Ch

un

, H

.C.,

Kin

g,

G.A

.,C

hu

ng

, C

.T.,

an

d D

ala

l, P

.S.

Ma

llin

ckro

dt

Inst

itute

of

Ra

dio

log

y (m

ulti

-si

te)

8332

Ca

nce

r19

8963

2421

-24

25P

rog

no

sis

in p

atie

nts

with

lo

cal

recu

rre

nce

aft

er

de

finiti

ve i

rra

dia

tion

fo

r p

rost

atic

ca

rcin

om

aK

ub

an

, D

.A.,

El-

Ma

hd

i, A

.M.,

an

dS

che

llha

mm

er,

P.F

.E

ast

ern

Vir

gin

ia M

ed

ica

l S

cho

ol

8333

Ca

nce

r19

8963

2415

-24

20I-

12

5 i

nte

rstit

ial

imp

lan

tatio

n f

or

pro

sta

te c

an

cer.

Wh

at

ha

ve w

e l

ea

rne

d 1

0 y

ea

rs l

ate

r?K

ub

an

, D

.A.,

El-

Ma

hd

i, A

.M.,

an

dS

che

llha

mm

er,

P.F

.E

ast

ern

Vir

gin

ia M

ed

ica

l S

cho

ol

8411

Jour

nal o

f U

rolo

gy19

8914

182

-84

Ca

use

-sp

eci

fic a

ctu

ari

al

surv

iva

l a

na

lysi

s: a

use

ful

me

tho

d f

or

rep

ort

ing

su

rviv

al

da

ta i

n m

en

with

clin

ica

lly l

oca

lize

d c

arc

ino

ma

of

the

pro

sta

teLe

po

r, H

., K

imb

all,

A.W

., a

nd

Wa

lsh

,P

.C.

Th

e J

oh

ns

Ho

pki

ns

Un

ive

rsity

an

dH

osp

ital

8428

Jour

nal o

f U

rolo

gy19

8914

156

4-56

6T

ota

l p

rost

ate

cto

my

for

clin

ica

lly l

oca

lize

dp

rost

atic

ca

nce

r: l

on

g-t

erm

re

sults

Gib

bo

ns,

R.P

., C

orr

ea

, R

.J.,

Jr.

, B

ran

ne

n,

G.E

., a

nd

We

issm

an

, R

.M.

Th

e V

irg

inia

Ma

son

Clin

ic

8493

Uro

logy

1989

3336

1-36

6P

rog

no

stic

sig

nifi

can

ce o

f D

NA

plo

idy

inca

rcin

om

a o

f p

rost

ate

De

jter,

S.W

., J

r.,

Cu

nn

ing

ha

m,

R.E

.,N

og

uch

i, P

.D.,

Jo

ne

s, R

.V.,

Mo

ul,

J.W

.,M

cLe

od

, D

.G.,

an

d L

ynch

, J.

H.

Ge

org

eto

wn

Un

ive

rsity

Ho

spita

l (m

ulti

-si

te)

8615

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1990

1913

83-

1388

Th

e r

ole

of

seru

m p

rost

atic

aci

d p

ho

sph

ata

se i

nth

e m

an

ag

em

en

t o

f a

de

no

carc

ino

ma

of

the

pro

sta

te w

ith r

ad

ioth

era

py

Ca

rlto

n,

J.C

., Z

ag

ars

, G

.K.,

an

d O

swa

ld,

M.J

.T

he

Un

ive

rsity

of

Te

xas

M.D

. A

nd

ers

on

Ca

nce

r C

en

ter

8616

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1990

1913

77-

1382

Th

e e

ffe

ct o

f o

vera

ll tr

ea

tme

nt

time

on

lo

cal

con

tro

l in

pa

tien

ts w

ith a

de

no

carc

ino

ma

of

the

pro

sta

te t

rea

ted

with

ra

dia

tion

th

era

py

Am

du

r, R

.J.,

Pa

rso

ns,

J.T

., F

itzg

era

ld,

L.T

., a

nd

Mill

ion

, R

.R.

Un

ive

rsity

of

Flo

rid

a C

olle

ge

of

Me

dic

ine

8717

Uro

logy

1990

3649

3-49

8R

ad

ica

l p

rost

ate

cto

my

vers

us

exp

ect

an

t p

rim

ary

tre

atm

en

t in

sta

ge

s I

an

d I

I p

rost

atic

ca

nce

r. A

fifte

en

-ye

ar

follo

w-u

p

Gra

vers

en

, P

.H.,

Nie

lse

n,

K.T

., G

ass

er,

T.C

., C

orl

e,

D.K

., a

nd

Ma

dse

n,

P.O

.V

ete

ran

s A

dm

inis

tra

tion

Ho

spita

l (m

ulti

-si

te)

8798

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1990

1956

1-56

8C

arc

ino

ma

of

the

pro

sta

te s

tag

e B

an

d C

: la

ck o

fin

flue

nce

of

du

ratio

n o

f ra

dio

the

rap

y o

n t

um

or

con

tro

l a

nd

tre

atm

en

t m

orb

idity

La

i, P

.P.,

Pe

rez,

C.A

., S

ha

pir

o,

S.J

., a

nd

Lo

cke

tt,

M.A

.M

alli

nck

rod

t In

stitu

te o

f R

ad

iolo

gy

(mu

lti-

site

)

8823

Jour

nal o

f U

rolo

gy19

9014

411

80-

1184

Ra

dic

al

pro

sta

tect

om

y fo

r cl

inic

al

sta

ge

T1

-2

N0

M0

pro

sta

tic a

de

no

carc

ino

ma

: lo

ng

-te

rmre

sults

Pa

uls

on

, D

.F.,

Mo

ul,

J.W

., a

nd

Wa

lthe

r,P

.J.

Du

ke U

niv

ers

ity M

ed

ica

l C

en

ter

8827

Jour

nal o

f U

rolo

gy19

9014

414

20-

1424

Ro

le o

f n

erv

e-s

pa

rin

g r

ad

ica

l p

rost

ate

cto

my

for

clin

ica

l st

ag

e B

2 p

rost

ate

ca

nce

rB

igg

, S

.W.,

Ka

vou

ssi,

L.R

., a

nd

Ca

talo

na

,W

.J.

Wa

shin

gto

n U

niv

ers

ity S

cho

ol

of

Me

dic

ine

89

02

Ra

dio

the

rap

y a

nd

On

colo

gy

19

90

18

235-

246

Ad

en

oca

rcin

om

a o

f th

e p

rost

ate

tre

ate

d w

ithe

xte

rna

l-b

ea

m r

ad

iatio

n t

he

rap

y: 5

-ye

ar

min

imu

mfo

llow

-up

Am

du

r, R

.J.,

Pa

rso

ns,

J.T

., F

itzg

era

ld,

L.T

., a

nd

Mill

ion

, R

.R.

Un

ive

rsity

of

Flo

rid

a C

olle

ge

of

Me

dic

ine

8925

Uro

log

ic C

linic

s o

f N

ort

hA

me

rica

1990

1777

9-78

5S

ele

ctio

n o

f p

atie

nts

with

sta

ge

B p

rost

ate

ca

nce

rfo

r ra

dic

al

pro

sta

tect

om

yM

idd

leto

n,

R.G

., L

ars

en

, R

.H.

Un

ive

rsity

of

Uta

h C

en

ter

for

the

He

alth

Sci

en

ces


Page A-9

Pa

pyr

us

Re

fere

nce

Jou

rna

lY

ea

rV

olP

ag

es

Titl

eA

utho

rsIn

stitu

tion

8990

Bri

tish

Jo

urn

al o

f U

rolo

gy

1990

6561

1-61

4T

he

na

tura

l co

urs

e o

f lo

w g

rad

e,

no

n-m

eta

sta

ticp

rost

atic

ca

rcin

om

aA

do

lfsso

n,

J.,

Ro

nst

rom

, L

., C

ars

ten

sen

,J.

, L

ow

ha

ge

n,

T.,

an

d H

ed

lun

d,

P.O

.K

aro

linsk

a H

osp

ital

(mu

lti-s

ite)

9175

Arc

hiv

es

of

Su

rge

ry19

9012

532

7-33

1S

tag

e B

pro

sta

te a

de

no

carc

ino

ma

. F

low

cyto

me

tric

nu

cle

ar

DN

A p

loid

y a

na

lysi

sM

on

tgo

me

ry,

B.T

., N

ativ

, O

., B

lute

, M

.L.,

Fa

rro

w,

G.M

., M

yers

, R

.P.,

Zin

cke

, H

.,T

he

rne

au

, T

.M.,

an

d L

ieb

er,

M.M

.

Ma

yo C

linic

9194

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1990

1831

5-32

0B

ow

el

com

plic

atio

ns

aft

er

rad

ioth

era

py

for

carc

ino

ma

of

the

pro

sta

te:

the

vo

lum

e e

ffe

ctM

am

eg

ha

n,

H.,

Fis

he

r, R

., M

am

eg

ha

n,

J.,

Wa

tt,

W.H

., a

nd

Tyn

an

, A

.In

stitu

te o

f R

ad

ioth

era

py

(mu

lti-s

ite)

9219

Uro

logy

1990

3522

3-22

7In

tra

op

era

tive

an

d e

arl

y co

mp

lica

tion

s o

f st

ag

ing

pe

lvic

lym

ph

no

de

dis

sect

ion

in

pro

sta

tica

de

no

carc

ino

ma

Do

no

hu

e,

R.E

., M

an

i, J.

H.,

Wh

itese

l, J.

A.,

Au

gsp

urg

er,

R.R

., W

illia

ms,

G.,

an

dF

auve

r, H

.E.

Un

ive

rsity

of

Co

lora

do

He

alth

Sci

en

ces

Ce

nte

r (m

ulti

-site

)

9265

Au

stra

lian

& N

ew

Ze

ala

nd

Jour

nal o

f S

urge

ry19

9161

658-

662

Ra

dia

tion

th

era

py

for

the

ma

na

ge

me

nt

of

loca

lize

d p

rost

ate

ca

rcin

om

aB

urm

eis

ter,

B.H

., P

rob

ert

, J.

C.

Au

ckla

nd

Ho

spita

l

9351

Ca

nce

r19

9167

1091

-10

96E

xpe

cta

nt

ma

na

ge

me

nt

of

loca

lize

d p

rost

atic

can

cer

Wh

itmo

re,

W.F

., J

r.,

Wa

rne

r, J

.A.,

an

dT

hom

pson

, I.M

., Jr

.M

em

ori

al

Slo

an

-Ke

tte

rin

g C

an

cer

Ce

nte

r

9407

Jour

nal o

f U

rolo

gy19

9114

551

2-51

4Im

pa

ct o

f a

na

tom

ica

l ra

dic

al

pro

sta

tect

om

y o

nu

rin

ary

co

ntin

en

ceS

tein

er,

M.S

., M

ort

on

, R

.A.,

an

d W

als

h,

P.C

.T

he

Jo

hn

s H

op

kin

s U

niv

ers

ity a

nd

Ho

spita

l95

72In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1985

1120

73-

2080

Imp

rovi

ng

th

e t

he

rap

eu

tic r

atio

of

ext

ern

al

be

am

irra

dia

tion

fo

r ca

rcin

om

a o

f th

e p

rost

ate

Fo

rma

n,

J.D

., Z

inre

ich

, E

., L

ee

, D

.J.,

Wh

ara

m,

M.D

., B

au

mg

ard

ne

r, R

.A.,

an

dO

rder

, S.E

.

Th

e J

oh

ns

Ho

pki

ns

Un

ive

rsity

an

dH

osp

ital

9580

Jour

nal o

f U

rolo

gy19

8513

349

-52

Op

era

ble

pro

sta

tic c

arc

ino

ma

: co

rre

latio

ns

am

on

gcl

inic

al

sta

ge

, p

ath

olo

gic

al

sta

ge

, G

lea

son

his

tolo

gic

al

sco

re a

nd

ea

rly

dis

ea

se-f

ree

su

rviv

al

Fo

wle

r, J

.E.,

Jr.

, M

ills,

S.E

.U

niv

ers

ity o

f V

irg

inia

Sch

oo

l o

f M

ed

icin

e

9717

Uro

logy

1983

2145

1-45

7P

elv

ic c

om

plic

atio

ns

aft

er

de

finiti

ve t

rea

tme

nt

of

pro

sta

te c

an

cer

by

inte

rstit

ial

or

ext

ern

al

be

am

rad

iatio

n

Sch

ellh

am

me

r, P

.F.,

El-

Ma

hd

i, A

.M.

Ea

ste

rn V

irg

inia

Me

dic

al

Sch

oo

l

9733

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1984

1054

1-54

8T

rip

le c

ou

rse

ext

ern

al

be

am

ra

dio

the

rap

y fo

rca

rcin

om

a o

f th

e p

rost

ate

El-

Ma

hd

i, A

.M.,

Tu

ralb

a,

C.I

.C.,

Sch

ellh

am

me

r, P

.F.,

an

d P

ee

ple

s, W

.J.E

ast

ern

Vir

gin

ia M

ed

ica

l S

cho

ol/M

ed

ica

lC

en

ter

Ho

spita

ls

9737

Jou

rna

l o

f th

e N

atio

na

l M

ed

ica

lA

sso

cia

tion

1984

7661

-66

Ext

ern

al

rad

iatio

n t

he

rap

y o

f lo

caliz

ed

pro

sta

ticca

nce

rR

ed

dy,

E.K

., G

iri,

S.,

an

d M

an

sfie

ld,

C.M

.U

niv

ers

ity o

f K

an

sas

Me

dic

al

Ce

nte

r(m

ulti

-site

)98

79In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1991

2153

7-54

7T

he

eff

ect

of

loca

l co

ntr

ol

on

me

tast

atic

dis

sem

ina

tion

in

ca

rcin

om

a o

f th

e p

rost

ate

: lo

ng

-te

rm r

esu

lts i

n p

atie

nts

tre

ate

d w

ith 1

25

Iim

pla

nta

tion

Fu

ks,

Z.,

Le

ibe

l, S

.A.,

Wa

llne

r, K

.E.,

Be

gg

, C

.B.,

Fa

ir,

W.R

., A

nd

ers

on

, L

.L.,

Hila

ris,

B.S

., a

nd

Wh

itmo

re,

W.F

.

Me

mo

ria

l S

loa

n-K

ett

eri

ng

Ca

nce

r C

en

ter

9895

Jour

nal o

f U

rolo

gy19

9114

511

97-

1200

Ca

nce

r co

ntr

ol

follo

win

g a

na

tom

ica

l ra

dic

al

pro

sta

tect

om

y: a

n i

nte

rim

re

po

rtM

ort

on

, R

.A.,

Ste

ine

r, M

.S.,

an

d W

als

h,

P.C

.T

he

Jo

hn

s H

op

kin

s U

niv

ers

ity a

nd

Ho

spita

l98

99Jo

urna

l of

Uro

logy

1991

146

798-

802

Co

mp

lica

tion

s fo

llow

ing

ext

ern

al

be

am

ra

dia

tion

the

rap

y fo

r p

rost

ate

ca

nce

r: a

n a

na

lysi

s o

f p

atie

nts

tre

ate

d w

ith a

nd

with

ou

t st

ag

ing

pe

lvic

lym

ph

ad

en

ect

om

y

Gre

sko

vich

, F

.J.,

Za

ga

rs,

G.K

., S

he

rma

n,

N.E

., an

d Jo

hnso

n, D

.E.

Un

ive

rsity

of

Te

xas

M.D

. A

nd

ers

on

Ca

nce

r C

en

ter

1003

9B

ritis

h J

ou

rna

l of

Uro

log

y19

9269

183-

187

De

ferr

ed

tre

atm

en

t in

clin

ica

lly l

oca

lise

d p

rost

atic

carc

ino

ma

Ad

olfs

son

, J.

, C

ars

ten

sen

, J.

, a

nd

Lo

wh

ag

en

, T

.K

aro

linsk

a H

osp

ital

(mu

lti-s

ite)

1007

6In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1992

2256

5-56

8T

he

eff

ica

cy o

f p

ha

rma

coki

ne

tic m

on

itori

ng

an

dd

ose

mo

difi

catio

n o

f e

tan

ida

zole

on

th

e i

nci

de

nce

of

ne

uro

toxi

city

: re

sults

fro

m a

ph

ase

II

tria

l o

fe

tan

ida

zole

an

d r

ad

iatio

n t

he

rap

y in

lo

cally

ad

van

ced

pro

sta

te c

an

cer

Co

lem

an

, C

.N.,

Bu

swe

ll, L

., N

oll,

L.,

Rie

se,

N.,

an

d R

ose

, M

.A.

Join

t C

en

ter

for

Ra

dia

tion

Th

era

py

(mu

lti-

site

)

1010

4Jo

urna

l of

Uro

logy

1992

147

905-

907

Th

e m

an

ag

em

en

t o

f re

cta

l in

jury

du

rin

g r

ad

ica

lre

tro

pu

bic

pro

sta

tect

om

yB

orl

an

d,

R.N

., W

als

h,

P.C

.T

he

Jo

hn

s H

op

kin

s U

niv

ers

ity a

nd

Ho

spita

l10

107

Jour

nal o

f U

rolo

gy19

9214

791

7-92

1T

he

im

po

rta

nce

of

loca

l co

ntr

ol

in t

he

tre

atm

en

to

f p

rost

atic

ca

nce

rK

ap

lan

, I.

D.,

Pre

stid

ge

, B

.R.,

Ba

gsh

aw

,M

.A.,

an

d C

ox,

R.S

.S

tan

ford

Un

ive

rsity

Sch

oo

l o

f M

ed

icin

e(m

ulti

-site

)10

108

Jour

nal o

f U

rolo

gy19

9214

788

8-89

0R

ad

ica

l p

rost

ate

cto

my:

th

e p

ros

an

d c

on

s o

f th

ep

eri

ne

al

vers

us

retr

op

ub

ic a

pp

roa

chF

razi

er,

H.A

., R

ob

ert

son

, J.

E.,

an

dP

au

lso

n,

D.F

.D

uke

Un

ive

rsity

Me

dic

al

Ce

nte

r


Page A-10

1010

9Jo

urna

l of

Uro

logy

1992

147

883-

887

Ra

dic

al

retr

op

ub

ic p

rost

ate

cto

my:

mo

rbid

ity a

nd

qu

alit

y o

f lif

e.

Exp

eri

en

ce w

ith 6

20

co

nse

cutiv

eca

ses

Le

an

dri

, P

., R

oss

ign

ol,

G.,

Ga

utie

r, J

.R.,

an

d R

am

on

, J.

Sa

int-

Jea

n L

an

gu

ed

oc-

Ce

rou

1018

3U

rolo

gy19

9239

44-4

7R

ad

ica

l p

rost

ate

cto

my:

OS

U a

nd

aff

ilia

ted

ho

spita

ls'

exp

eri

en

ce 1

98

5-1

98

9D

rag

o,

J.R

., B

ad

ala

me

nt,

R.A

., Y

ork

, J.

P.,

Sim

on

, J.

, R

iem

en

sch

ne

ide

r, H

., N

esb

itt,

J.A

., a

nd

Pe

rez,

J.

Oh

io S

tate

Un

ive

rsity

(m

ulti

-site

)

1018

4Jo

urn

al

of

the

Am

eri

can

Me

dic

al

Ass

oci

atio

n19

9226

721

91-

2196

Hig

h 1

0-y

ea

r su

rviv

al

rate

in

pa

tien

ts w

ith e

arl

y,u

ntr

ea

ted

pro

sta

tic c

an

cer

Joh

an

sso

n,

J.E

, A

da

mi,

H.O

., A

nd

ers

son

,S

.O.,

Be

rgst

rom

, R

., H

olm

be

rg,

L.,

Kru

sem

o, U

.B.

Ore

bro

Me

dic

al

Ce

nte

r H

osp

ital

(mu

lti-

site

)

10

25

1E

uro

pe

an

Uro

log

y1

99

32

41-

6O

utc

om

e o

f p

atie

nts

with

un

tre

ate

d c

an

cer

of

the

pro

sta

teS

ten

zl,

A.,

Stu

de

r, U

.E.

Un

ive

rsity

of

Be

rne

Me

dic

al

Ce

nte

r

1030

3S

can

din

avi

an

Jo

urn

al

of

Uro

log

y &

Ne

ph

rolo

gy

1993

2721

9-22

4R

ad

ica

l re

tro

pu

bic

pro

sta

tect

om

y fo

r lo

calis

ed

pro

sta

tic c

arc

ino

ma

: a

clin

ica

l a

nd

pa

tho

log

ica

lst

ud

y o

f 2

01

ca

ses

Pe

de

rse

n,

K.V

., H

erd

er,

A.

Un

ive

rsity

Ho

spita

l

1031

0C

an

cer

1993

7217

09-

1725

Pro

gn

ost

ic f

act

ors

in

pro

sta

te c

an

cer.

An

aly

sis

of

87

4 p

atie

nts

tre

ate

d w

ith r

ad

iatio

n t

he

rap

yZ

ag

ars

, G

.K.,

vo

n-E

sch

en

ba

ch,

A.C

., a

nd

Aya

la,

A.G

.T

he

Un

ive

rsity

of

Te

xas

M.D

. A

nd

ers

on

Ca

nce

r C

en

ter

1032

2Jo

urna

l of

Uro

logy

1993

150

905-

907

Re

turn

of

ere

ctio

ns

an

d u

rin

ary

co

ntin

en

cefo

llow

ing

ne

rve

sp

ari

ng

ra

dic

al

retr

op

ub

icp

rost

ate

cto

my

Ca

talo

na

, W

.J.,

Ba

sle

r, J

.W.

Wa

shin

gto

n U

niv

ers

ity S

cho

ol

of

Me

dic

ine

1034

0C

an

cer

1993

7212

91-

1299

Tra

nsr

ect

al

ultr

aso

un

d-g

uid

ed

pe

rcu

tan

eo

us

rad

ica

l cr

yosu

rgic

al

ab

latio

n o

f th

e p

rost

ate

On

ik,

G.M

., C

oh

en

, J.

K.,

Re

yes,

G.D

.,R

ub

insk

y, B

., C

ha

ng

, Z

., a

nd

Ba

ust

, J.

Alle

gh

en

y G

en

era

l H

osp

ital

(mu

lti-s

ite)

1036

9In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1993

2658

1-59

1T

ech

nic

al

an

d t

um

or-

rela

ted

fa

cto

rs a

ffe

ctin

go

utc

om

e o

f d

efin

itive

irr

ad

iatio

n f

or

loca

lize

dca

rcin

om

a o

f th

e p

rost

ate

Pe

rez,

C.A

., L

ee

, H

.K.,

Ge

org

iou

, A

.,L

og

sdo

n,

M.D

., L

ai,

P.P

., a

nd

Lo

cke

tt,

M.A

.

Ma

llin

ckro

dt

Inst

itute

of

Ra

dio

log

y (m

ulti

-si

te)

1037

3U

rolo

gy19

9342

13-2

0P

rost

ate

-sp

eci

fic a

ntig

en

to

de

term

ine

pro

gre

ssio

n-

fre

e s

urv

iva

l a

fte

r ra

dia

tion

th

era

py

for

loca

lize

dca

rcin

om

a o

f p

rost

ate

Sch

ellh

am

me

r, P

.F.,

El-

Ma

hd

i, A

.M.,

Wri

gh

t, G

.L.,

Jr.

, K

olm

, P

., a

nd

Ra

gle

, R

.Th

e C

en

ter

for

Uro

log

ic O

nco

log

y o

fE

ast

ern

Vir

gin

ia M

ed

ica

l S

cho

ol

(mu

lti-

site

)10

517

Uro

logy

1993

4112

2-12

6Io

din

e-1

25

se

ed

im

pla

nts

fo

r p

rost

atic

ca

rcin

om

a.

Fiv

e-

an

d t

en

-ye

ar

follo

w-u

pW

eyr

ich

, T

.P.,

Ka

nd

zari

, S

.J.,

an

d J

ain

,P

.R.

We

st V

irg

inia

Un

ive

rsity

Me

dic

al

Ce

nte

r

1055

0In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1993

2620

3-21

0C

arc

ino

ma

of

the

pro

sta

te:

resu

lts o

f ra

dic

al

rad

ioth

era

py

(19

70

-19

85

)D

un

can

, W

., W

ard

e,

P.,

Ca

tto

n,

C.N

.,M

un

ro,

A.J

., L

aki

er,

R.,

Ga

da

lla,

T.,

an

dG

osp

od

aro

wic

z, M

.K.

Pri

nce

ss M

arg

are

t H

osp

ital

1067

2R

ece

nt

Re

sults

in

Ca

nce

rR

ese

arc

h19

9312

643

-49

Ra

dic

al

pro

sta

tect

om

y fo

r ca

rcin

om

a o

f th

ep

rost

ate

: lo

ng

-te

rm r

esu

ltsF

roh

mu

ller,

H.G

.W.,

Wir

th,

M.P

.U

rolo

gis

che

Klin

ik u

nd

Po

liklin

ik (

mu

lti-

site

)10

693

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1993

2566

1-66

7S

ho

rt-t

erm

mo

rbid

ity f

rom

CT

-pla

nn

ed

tra

nsp

eri

ne

al

I-1

25

pro

sta

te i

mp

lan

tsA

rte

rbe

ry,

V.E

., W

alln

er,

K.,

Ro

y, J

., a

nd

Fu

ks,

Z.

Me

mo

ria

l S

loa

n-K

ett

eri

ng

Ca

nce

r C

en

ter

1074

8Jo

urn

al

of

the

Na

tion

al

Me

dic

al

Ass

oci

atio

n19

9385

109-

112

Pro

sta

te c

an

cer:

re

sults

of

ext

ern

al

irra

dia

tion

Re

dd

y, E

.K.,

Kri

shn

an

, L

., G

iri,

S.,

Eva

ns,

R.G

., M

eb

ust

, W

.K.,

an

d W

eig

el,

J.W

.U

niv

ers

ity o

f K

an

sas

Me

dic

al

Ce

nte

r

1079

0Jo

urna

l of

Uro

logy

1993

149

519-

522

Pro

sta

te s

pe

cific

an

tige

n a

fte

r e

xte

rna

l b

ea

mra

dio

the

rap

y fo

r p

rost

atic

ca

nce

r: f

ollo

wu

pK

ap

lan

, I.

D.,

Co

x, R

.S.,

an

d B

ag

sha

w,

M.A

.S

tan

ford

Un

ive

rsity

Me

dic

al

Ce

nte

r

1106

2S

can

din

avi

an

Jo

urn

al

of

Uro

log

y &

Ne

ph

rolo

gy

1992

2623

1-23

4R

ad

ica

l re

tro

pu

bic

pro

sta

tect

om

y: o

ur

exp

eri

en

cew

ith t

he

fir

st 5

4 p

atie

nts

Se

rvo

ll, E

., H

alv

ors

en

, O

.J.,

Ha

uka

as,

S.,

an

d H

ois

ae

ter,

P.A

.H

au

kela

nd

Un

ive

rsity

Ho

spita

l

1110

4H

en

ry F

ord

Ho

spita

l M

ed

ica

lJo

urn

al

1992

4010

8-11

0R

ad

ica

l su

rge

ry i

n t

he

tre

atm

en

t o

f lo

caliz

ed

carc

ino

ma

of

the

pro

sta

teT

ela

ng

, D

.J.,

Mile

s, B

.J.,

Fa

rah

, R

.N.,

Litt

leto

n,

R.H

., K

irke

mo

, A

.K.,

Pe

ab

od

y,J.

O.,

Bu

rks,

D.A

., F

lem

ing

, C

., a

nd

Ce

rny,

J.C

.

He

nry

Fo

rd H

osp

ital

1110

8E

uro

pe

an

Jo

urn

al

of

Su

rgic

al

On

colo

gy

1992

1845

6-46

2R

ad

ica

l p

rost

ate

cto

my

for

loca

lize

d p

rost

ate

can

cer

Va

n-P

op

pe

l, H

., A

me

ye,

F.,

Oye

n,

R.,

Va

n-d

e-V

oo

rde

, W

., a

nd

Ba

ert

, L

.U

niv

ers

ity H

osp

itals

of

the

Ka

tho

lieke

Un

ive

rsite

it11

201

Inte

rna

tion

al

Jou

rna

l o

fR

ad

iatio

n O

nco

log

y, B

iolo

gy,

Ph

ysic

s

1992

2448

5-48

8C

on

form

al

sta

tic f

ield

ra

dia

tion

th

era

py

tre

atm

en

to

f e

arl

y p

rost

ate

ca

nce

r ve

rsu

s n

on

-co

nfo

rma

lte

chn

iqu

es:

a r

ed

uct

ion

in

acu

te m

orb

idity

So

ffe

n,

E.M

., H

an

ks,

G.E

., H

un

t, M

.A.,

an

d E

pst

ein

, B

.E.

Fo

x C

ha

se C

an

cer

Ce

nte

r

1140

0U

rolo

gy19

9240

18-2

6R

ad

iatio

n t

he

rap

y in

pro

sta

te c

an

cer:

wh

ole

pe

lvis

with

pro

sta

te b

oo

st o

r sm

all

field

to

pro

sta

te?

Plo

yso

ng

san

g,

S.S

., A

ron

, B

.S.,

an

dS

he

ha

ta,

W.M

.T

he

Ch

rist

Ho

spita

l (m

ulti

-site

)


Page A-11

Pa

pyr

us

Re

fere

nce

Jou

rna

lY

ea

rV

olP

ag

es

Titl

eA

utho

rsIn

stitu

tion

1140

2R

ad

iolo

gy

1992

184

333-

339

Re

sults

of

rad

ica

l p

eri

ne

al

pro

sta

tect

om

y w

itha

dju

van

t b

rach

yth

era

py

Do

orn

bo

s, J

.F.,

Hu

sse

y, D

.H.,

Ro

bin

son

,R

.A.,

We

n,

B.C

., a

nd

Vig

liott

i, A

.P.

Un

ive

rsity

of

Iow

a C

olle

ge

of

Me

dic

ine

(mu

lti-s

ite)

1151

1In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1992

2329

3-29

8C

om

pa

riso

n o

f p

ath

olo

gic

an

d c

linic

al

eva

lua

tion

of

lym

ph

no

de

s in

pro

sta

te c

an

cer:

im

plic

atio

ns

of

RT

OG

da

ta f

or

pa

tien

t m

an

ag

em

en

t a

nd

tri

al

de

sig

n a

nd

str

atif

ica

tion

Ha

nks

, G

.E.,

Kra

ll, J

.M.,

Pile

pic

h,

M.V

.,A

sbe

ll, S

.O.,

Pe

rez,

C.A

., R

ub

in,

P.,

Sa

use

, W

.T.,

an

d D

og

ge

tt,

R.L

.S.

Fo

x C

ha

se C

an

cer

Ce

nte

r (m

ulti

-site

)

1164

5In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1992

2293

5-93

9T

ran

spe

rin

ea

l p

erc

uta

ne

ou

s ir

idiu

m-1

92

in

ters

titia

lte

mp

late

im

pla

nt

of

the

pro

sta

te:

resu

lts a

nd

com

plic

atio

ns

in 3

21

pa

tien

ts

Kh

an

, K

., T

ho

mp

son

, W

., B

ush

, S

., a

nd

Stid

ley,

C.

Un

ive

rsity

of

Ne

w M

exi

co C

an

cer

Ce

nte

r(m

ulti

-site

)

1171

0S

can

din

avi

an

Jo

urn

al

of

Uro

log

y a

nd

Ne

ph

rolo

gy

-S

up

ple

me

ntu

m

1991

138

109-

115

Lo

ng

te

rm r

esu

lts o

f u

ltra

son

ica

lly g

uid

ed

imp

lan

tatio

n o

f 1

25

-I s

ee

ds

com

bin

ed

with

ext

ern

al

irra

dia

tion

in

lo

caliz

ed

pro

sta

tic c

an

cerIv

ers

en

, P

., R

asm

uss

en

, F

., a

nd

Ho

lm,

H.H

.H

erl

ev

Ho

spita

l (m

ulti

-site

)

1185

0S

can

din

avi

an

Jo

urn

al

of

Uro

log

y a

nd

Ne

ph

rolo

gy

-S

up

ple

me

ntu

m

1991

137

113-

118

Tra

nsp

eri

ne

al

ultr

aso

un

d-g

uid

ed

im

pla

nta

tion

of

the

pro

sta

te:

mo

rbid

ity a

nd

co

mp

lica

tion

sB

lask

o,

J.C

., R

ag

de

, H

., a

nd

Gri

mm

, P

.D.

No

rth

we

st T

um

or

Inst

itute

1187

5Jo

urna

l of

Uro

logy

1991

146

1317

-13

19F

ailu

re o

f o

pe

n r

ad

ioa

ctiv

e 1

25

iod

ine

imp

lan

tatio

n t

o c

on

tro

l lo

caliz

ed

pro

sta

te c

an

cer:

a s

tud

y o

f 4

1 p

atie

nts

Go

tte

sma

n,

J.E

., T

esh

, D

.G.,

an

dW

eis

sma

n,

W.D

.T

he

Tu

mo

r In

stitu

te o

f th

e S

we

dis

hH

osp

ital

Me

dic

al

Ce

nte

r

1193

6In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1991

2195

5-96

0E

xte

rna

l b

ea

m i

rra

dia

tion

ve

rsu

s12

5 io

din

e i

mp

lan

tin

th

e d

efin

itive

tre

atm

en

t o

f p

rost

ate

ca

rcin

om

aKo

pro

wsk

i, C

.D.,

Be

rke

nst

ock

, K

.G.,

Bo

rofs

ki,

A.M

., Z

ieg

ler,

J.C

., L

igh

tfo

ot,

D.A

., a

nd

Bra

dy,

L.W

.

Co

op

er

Ho

spita

l/Un

ive

rsity

Me

dic

al

Ce

nte

r (m

ulti

-site

)

1193

9In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1991

2193

5-93

9L

on

g-t

erm

tre

atm

en

t se

qu

ela

e f

ollo

win

g e

xte

rna

lb

ea

m i

rra

dia

tion

fo

r a

de

no

carc

ino

ma

of

the

pro

sta

te:

an

aly

sis

of

RT

OG

stu

die

s 7

50

6 a

nd

77

06

La

wto

n,

C.A

., W

on

, M

., P

ilep

ich

, M

.V.,

Asb

ell,

S.O

., S

hip

ley,

W.U

., H

an

ks,

G.E

.,C

ox,

J.D

., P

ere

z, C

.A.,

Sa

use

, W

.T.,

Do

gg

ett

, S

.R.,

an

d R

ub

in,

P.

Me

dic

al

Co

lleg

e o

f W

isco

nsi

n (

mu

lti-

site

)

1194

1In

tern

atio

na

l Jo

urn

al

of

Ra

dia

tion

On

colo

gy,

Bio

log

y,P

hys

ics

1991

2110

99-

1103

Ou

tco

me

fo

r ly

mp

h n

od

e d

isse

ctio

n n

eg

ativ

e T

-1b

,T

-2 (

A-2

,B)

pro

sta

te c

an

cer

tre

ate

d w

ith e

xte

rna

lb

ea

m r

ad

iatio

n t

he

rap

y in

RT

OG

77

06

Ha

nks

, G

.E.,

Asb

ell,

S.,

Kra

ll, J

.M.,

Pe

rez,

C.A

., D

og

ge

tt,

S.,

Ru

bin

, P

.,S

au

se,

W.,

an

d P

ilep

ich

, M

.V.

Un

ive

rsity

of

Pe

nn

sylv

an

ia/F

ox

Ch

ase

Ca

nce

r C

en

ter

(mu

lti-s

ite)

1194

6E

uro

pe

an

Uro

log

y19

9119

279-

283

Ra

dic

al

pro

sta

tect

om

y fo

r ca

rcin

om

a o

f th

ep

rost

ate

: lo

ng

-te

rm f

ollo

w-u

p o

f 1

15

pa

tien

tsF

roh

mu

ller,

H.,

Th

eis

s, M

., a

nd

Wir

th,

M.P

.U

niv

ers

ity o

f W

urz

bu

rg M

ed

ica

l S

cho

ol

1197

2Jo

urna

l of

Uro

logy

1991

146

1040

-10

45T

he

ris

k o

f d

yin

g o

f p

rost

ate

ca

nce

r in

pa

tien

tsw

ith c

linic

ally

lo

caliz

ed

dis

ea

seL

ern

er,

S.P

., S

ea

le-H

aw

kin

s, C

., C

arl

ton

,C

.E.,

Jr.

, a

nd

Sca

rdin

o,

P.T

.B

ayl

or

Co

lleg

e o

f M

ed

icin

e (

mu

lti-s

ite)

1221

0E

uro

pe

an

Uro

log

y19

9018

117-

119

Ext

ern

al-

be

am

ra

dia

tion

fo

r ca

rcin

om

a o

f th

ep

rost

ate

Da

vie

s, A

.H.,

Da

vis,

H.L

., R

am

ara

kha

, P

.,D

urr

an

t, K

.D.,

an

d F

ello

ws,

G.J

.C

hu

rch

ill H

osp

ital

1224

1S

ou

th A

fric

an

Me

dic

al

Jou

rna

l199

078

309-

311

Ra

dic

al

irra

dia

tion

fo

r ca

rcin

om

a o

f th

e p

rost

ateA

bra

tt,

R.P

., C

raig

he

ad

, P

.S.,

Re

dd

i, V

.B.,

an

d S

are

mb

ock

, L

.A.

Un

ive

rsity

of

Ca

pe

To

wn

an

d G

roo

teS

chu

ur

Ho

spita

l (m

ulti

-site

)12

322

Uro

logy

1990

3537

7-38

0R

ad

ica

l p

rost

ate

cto

my

19

72

-19

87

sin

gle

inst

itutio

na

l e

xpe

rie

nce

: co

mp

ari

son

of

sta

nd

ard

rad

ica

l p

rost

ate

cto

my

an

d n

erv

e-s

pa

rin

g t

ech

niq

ue

Dra

go

, J.

R.,

Ba

da

lam

en

t, R

.A.,

an

dN

esbi

tt, J

.A.

Co

lleg

e o

f M

ed

icin

e,

Oh

io S

tate

Un

ive

rsity

1234

3Jo

urn

al

of

the

Na

tion

al

Me

dic

al

Ass

oci

atio

n19

9082

181-

193

Iod

ine

-12

5 i

nte

rstit

ial

irra

dia

tion

fo

r lo

caliz

ed

pro

sta

te c

an

cer

Ku

ma

r, P

.P.,

Go

od

, R

.R.,

an

d B

art

on

e,

F.F

.U

niv

ers

ity o

f N

eb

rask

a C

olle

ge

of

Me

dic

ine

1237

4Jo

urna

l of

Uro

logy

1990

143

538-

544

Ne

rve

-sp

ari

ng

ra

dic

al

pro

sta

tect

om

y: e

valu

atio

n o

fre

sults

aft

er

25

0 p

atie

nts

Ca

talo

na

, W

.J.,

Big

g,

S.W

.W

ash

ing

ton

Un

ive

rsity

Sch

oo

l o

fM

ed

icin

e12

404

Bri

tish

Jo

urn

al o

f U

rolo

gy

1989

6451

1-51

5E

arl

y p

ost

-op

era

tive

mo

rbid

ity o

f to

tal

pro

sta

tect

om

yR

itch

ie,

A.W

.S.,

Ja

me

s, K

., a

nd

de

Ke

rnio

n,

J.B

.U

CL

A S

cho

ol

of

Me

dic

ine

1244

2Jo

urna

l of

Uro

logy

1989

142

1227

-12

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on

tine

nce

fo

llow

ing

ne

rve

-sp

ari

ng

ra

dic

al

pro

sta

tect

om

yO

'Do

nn

ell,

P.D

., F

ina

n,

B.F

.V

ete

ran

s A

dm

inis

tra

tion

Me

dic

al

Ce

nte

r

1253

9C

an

cer

1989

6324

15-

2420

I-1

25

in

ters

titia

l im

pla

nta

tion

fo

r p

rost

ate

ca

nce

r.W

ha

t h

ave

we

le

arn

ed

10

ye

ars

la

ter?

Ku

ba

n,

D.A

., E

l-M

ah

di,

A.M

., a

nd

Sch

ellh

am

me

r, P

.F.

Ea

ste

rn V

irg

inia

Me

dic

al

Sch

oo

l


Page A-12

Ra

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0.5

%1

17

53

.0%

12

Mo

d,

Gle

aso

ns

(5

-7)

165

6.9

%92

813

40

.6%

510

135

1.3

%57

25

34

.8%

140

Lo

w,

Gle

aso

ns

(2

-4)

16

23

.1%

37

61

34

1.2

%5

17

13

38

.3%

42

75

62

.2%

25

0T

ota

l:1

,63

1T

ota

l:1

,25

6T

ota

l:1

,11

6T

ota

l:40

2

DN

A C

ON

TE

NT

Da

ta1

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

S%

yx

yS

% y

xy

S%

yx

yS

% y

xy

An

eu

plo

id3

4.2

%14

336

00

0T

etr

ap

loid

12

8.4

%74

261

00

0D

iplo

id3

73

.8%

24

83

36

00

0

Page A-13

Tabl

e A

-3.

Des

crip

tive

data

ana

lysi

s


Page A-14

Ra

dia

tion

:R

ad

iatio

n:

Ra

dic

al

Pro

sta

tect

om

yE

xte

rna

l B

ea

mB

rach

yth

era

py

(In

ters

titia

l)S

urv

eill

an

ce

PA

TH

OL

OG

Y D

ata

1

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

S%

yx

yS

% y

xy

S%

yx

yS

% y

xy

Ca

psu

le p

en

etr

atio

n12

38

.3%

443

1,1

56

00

0P

os.

ca

psu

le m

arg

in8

30

.0%

186

619

00

0P

os.

se

min

al

vesi

cle

s13

19

.2%

192

1,0

02

00

0P

os.

bla

dd

er

ne

ck4

18

.9%

5428

50

00

Po

s. u

reth

ral

ma

rgin

32

2.5

%6

22

76

00

0

PR

OG

RE

SS

ION

De

finiti

on

Da

ta1

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

S%

yx

yS

% y

xy

S%

yx

yS

% y

xy

DR

E (

en

larg

ing

ma

ss)

71

00

%41

241

238

10

0%

1,6

43

1,6

43

106

4%

150

236

71

00

%15

915

9L

oca

l sy

mp

tom

s4

10

0%

335

335

251

00

%40

740

79

10

0%

4444

50

%0

0R

isin

g P

AP

99

0%

337

376

259

2%

595

648

70

%0

02

10

0%

159

159

Ris

ing

PS

A4

10

0%

7777

50

%0

407

50

%0

00

TR

US

/BX

21

00

%47

479

10

0%

3939

79

6%

363

379

0B

iop

sy w

/wo

TR

US

30

%0

015

72

%1

86

26

04

58

%4

68

00

Ca

on

Re

-TU

RP

(S

tag

e A

)0

50

%0

407

00

Bo

ne

sca

n p

rog

.10

56

%49

8823

90

%41

846

39

0%

00

61

00

%12

212

2C

T p

rog

ress

ion

30

%0

07

0%

00

10

%0

00

MR

I p

rog

ress

ion

04

0%

04

07

00

DE

MO

GR

AP

HIC

Da

ta

To

tal

nu

mb

er

of

seri

es

2S

59S

84S

43S

8M

ea

n a

ge

(ye

ars

)34

62.7

2965

.925

64.5

770

Min

imu

m a

ge

(ye

ars

)34

.026

.036

.038

.0M

axi

mu

m a

ge

(ye

ars

)84

.092

.091

.090

.0N

um

be

r o

f p

atie

nts

577

,59

583

11

,46

543

3,9

12

862

3M

ea

n F

/U (

mo

nth

s)12

70.2

2670

.321

56.5

711

1.6

Min

imu

m F

/U (

mo

nth

s)1.

01.

01.

03.

0M

axi

mu

m F

/U (

mo

nth

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2.0

264.

021

9.0

298.

0

FO

LL

OW

-UP

Da

ta1

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

Re

po

rtin

g S

eri

es

S%

yx

yS

% y

xy

S%

yx

yS

% y

xy

Nu

mb

er

with

5 y

r F

/U20

61

.0%

1,1

88

1,9

49

256

2.2

%1

,80

22

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715

72

.4%

642

887

68

7.5

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045

7N

um

be

r w

ith 1

0 y

r F

/U16

50

.9%

759

1,4

92

89

.7%

110

1,1

32

41

9.2

%10

052

25

19

.7%

4623

4N

um

be

r w

ith 1

5 y

r F

/U14

43

.6%

530

1,2

16

00

43

4.7

%33

95

1 Th

e l

ett

er

x d

esi

gn

ate

s a

pp

lica

ble

nu

mb

er

of

pa

tien

ts,

the

le

tte

r y

tota

l n

um

be

r o

f p

atie

nts

. F

or

calc

ula

ting

pe

rce

nta

ge

s, x

is

the

nu

me

rato

r, y

th

e d

en

om

ina

tor.

2 Th

e t

erm

"se

rie

s" d

en

ote

s p

atie

nt

gro

up

s st

ratif

ied

by

pa

rtic

ula

r p

ara

me

ters

su

ch a

s st

ag

e o

f d

ise

ase

an

d t

rea

tme

nt

mo

da

lity.

On

e a

rtic

le m

ay

ha

ve m

ore

th

an

on

e s

eri

es.

3 Th

e s

tag

e c

od

es

for

this

da

tab

ase

are

:A

A (

No

A1

-A2

se

pa

ratio

n)

B3

B3

(B

ilat.

dis

ea

se)

BT

(B

Te

tra

plo

id)

L (

Lo

caliz

ed

A-B

)A

2 (

Sta

ge

A2

)B

A B

(A

ne

up

loid

)C

(C

Clin

ica

l &

C P

ath

olo

gic

)L

R (

Lo

caliz

ed

re

gio

na

l)B

(S

tag

e B

)B

C (

B C

linic

al)

CC

(C

Clin

ica

l)O

Oth

er,

de

fine

:B

1 B

1 (

if se

pa

rab

le)

BD

(B

Dip

loid

)D

(A

ll st

ag

e D

)R

Re

curr

en

ce-e

.g.,

fo

llow

ing

tre

atm

en

t b

y R

RP

or

RT

B2

B2

(if

sep

ara

ble

)B

P (

Pa

tho

log

ic B

)K

(C

om

plic

atio

n/C

ost

da

ta)

U U

nkno

wn


Page A-15

Ra

dic

al

Pro

sta

tect

om

y 1

Ra

dia

tio

n:

E

xte

rna

l B

ea

m2

Ra

dia

tio

n:

B

rach

yth

era

py

3S

urv

eil

lan

ce4

(In

ters

titi

al

Ra

dio

the

rap

y)P

ap

yru

sS

tag

eA

rmR

xY

ea

rS

urv

iva

lP

ap

yru

sS

tag

eA

rmR

xY

ea

rS

urv

iva

lP

ap

yru

sS

tag

eA

rmR

xY

ea

rS

urv

iva

lP

ap

yru

sS

tag

eA

rmR

xY

ea

rS

urv

iva

lO

VE

RA

LL S

UR

VIV

AL

OV

ER

ALL

SU

RV

IVA

LO

VE

RA

LL S

UR

VIV

AL

OV

ER

ALL

SU

RV

IVA

L12

81L

1A

B5

68.9

1221

0L

1B

AA

551

.411

710

L0

BB

BA

557

.010

184

L0

D5

67.0

8717

B1

A5

75.0

8318

B1

BA

555

.074

19B

1B

BA

B5

65.0

1025

1L

1D

567

.084

11B

1A

B5

82.0

2690

B3

1B

A5

60.0

7671

B2

1B

BA

A5

74.0

1003

9B

1D

580

.043

45B

21

A5

83.0

3195

B3

1B

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60.0

1234

3L

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BB

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78.5

9351

B2

1D

584

.091

75B

A1

AA

585

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511

BP

2B

A5

61.0

1197

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84.0

9351

B3

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584

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75B

D1

AA

585

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02B

21

BA

566

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936

L2

BB

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586

.087

17B

2D

585

.091

75B

T1

AA

585

.075

22B

1B

A5

68.0

1164

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11

BB

AC

589

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51B

11

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92.0

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590

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11

BA

569

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70B

1B

BA

B5

93.0

1025

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1034

.098

95L

0A

AA

593

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19B

1B

A5

70.0

1018

4L

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1041

.011

402

BP

1A

B5

95.0

7765

B1

BA

571

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RO

GR

ES

SIO

N -

FR

EE

SU

RV

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L10

039

B1

D10

50.0

1281

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AB

1044

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77B

1B

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72.0

1171

0L

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BA

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38.0

8717

B2

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60.0

8717

B1

A10

48.0

1078

L1

BA

572

.076

71B

21

BB

AA

552

.093

51B

0D

1070

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11B

1A

B10

70.0

6935

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BA

575

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BB

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555

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17B

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1539

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BP

1A

B10

70.0

6732

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1B

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76.0

1164

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BA

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69.0

9351

B2

1D

1539

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75B

1A

A10

75.1

7164

B1

BA

576

.083

33B

22

BB

AA

577

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51B

31

D15

63.0

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B1

AA

1078

.026

90B

21

BA

577

.012

539

BP

1B

BA

A5

77.0

9351

B1

1D

1567

.088

23L

1A

1088

.031

95B

21

BA

577

.010

373

B2

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BA

A5

78.0

1281

L1

AB

1522

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511

B1

BA

577

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42B

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B5

80.0

PR

OG

RE

SS

ION

- F

RE

E S

UR

VIV

AL

8717

B1

A15

25.0

7164

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BA

578

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10B

1B

B5

84.0

1018

4B

0D

568

.091

75B

A1

AA

1555

.081

61B

1B

A5

78.0

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B1

BB

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584

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184

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53.0

8411

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AB

1556

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41B

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AA

579

.076

70B

1B

BA

B5

86.0

8823

L1

A15

60.0

8798

B0

BA

A5

80.0

8333

B1

2B

BA

A5

88.0

ME

TA

ST

AS

IS -

FR

EE

SU

RV

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L91

75B

D1

AA

1565

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107

B2

1B

A5

80.0

1253

9B

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BA

A5

88.0

No

Da

ta91

75B

T1

AA

1570

.011

511

B2

BA

580

.010

373

B1

2B

BA

A5

90.0

8182

B1

AA

1575

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63B

1B

A5

81.0

8333

B2

2B

BA

A10

50.0

DIS

EA

SE

- S

PE

CIF

IC S

UR

VIV

AL

5219

B1

BA

582

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539

B2

1B

BA

A10

50.0

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589

.0P

RO

GR

ES

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N -

FR

EE

SU

RV

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L10

550

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BA

582

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373

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55.0

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594

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B1

AB

581

.926

90B

11

BA

583

.076

44B

1B

BA

A10

62.0

1003

9B

1D

599

.081

82B

1A

A5

92.0

3195

B1

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83.0

8333

B1

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BA

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88.0

1003

9B

1D

1084

.081

82B

1A

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82.0

6937

B1

BA

584

.012

539

B1

1B

BA

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88.0

1018

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0D

1085

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82B

1A

A15

70.0

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0B

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AA

584

.010

373

B1

2B

BA

A10

90.0

1025

1L

1D

1085

.011

511

BP

1B

A5

84.0

ME

TA

ST

AS

IS -

FR

EE

SU

RV

IVA

L12

241

L1

BA

585

.0M

ET

AS

TA

SIS

- F

RE

E S

UR

VIV

AL

No

Da

ta83

31B

C0

BA

586

.0N

o Da

ta11

941

L1

BA

587

.0D

ISE

AS

E -

SP

EC

IFIC

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L11

936

L1

BA

589

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AS

E -

SP

EC

IFIC

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RV

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L91

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AA

590

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590

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592

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82B

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95.0

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591

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343

L1

BB

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593

.291

75B

D1

AA

596

.077

96B

1B

A5

93.0

7419

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BB

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510

0.0

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BT

1A

A5

96.0

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1041

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95L

0A

AA

597

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35B

1B

A10

46.0

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1091

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78L

1B

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48.0

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1088

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31B

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1048

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82B

1A

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93.0

6937

B1

BA

1053

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75B

A1

AA

1555

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550

B1

BA

1054

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75B

D1

AA

1590

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32B

21

BA

1055

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75B

T1

AA

1590

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310

B1

BA

A10

57.0

8182

B1

AA

1593

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107

B2

1B

A10

60.0

8411

B1

AB

1587

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941

L1

BA

1063

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96B

1B

A10

70.0

6732

B2

1B

A15

31.0

1031

0B

1B

AA

1533

.0

Tabl

e A

-4. A

ctua

rial s

urvi

val d

ata

for

circ

le g

raph

s


Page A-16

Ra

dia

tio

n:

Ext

ern

al

Be

am

2

Pa

pyr

us

Re

f.S

tag

eA

rmR

xY

ea

rS

urv

iva

l%

PR

OG

RE

SS

ION

- F

RE

E S

UR

VIV

AL

1151

1B

P2

BA

532

.026

90B

31

BA

538

.031

95B

31

BA

538

.092

65B

1B

AA

548

.061

41B

1B

AA

549

.011

511

B2

BA

555

.040

76B

C1

BA

559

.010

373

B1

1B

A5

60.0

1037

3B

21

BA

560

.011

511

B1

BA

563

.071

64B

1B

A5

64.0

7164

B2

BA

564

.069

35B

1B

A5

66.0

2690

B2

1B

A5

68.0

3195

B2

1B

A5

68.0

1140

0B

1B

A5

68.0

6937

B1

BA

571

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33B

21

BA

A5

72.0

1151

1B

P1

BA

572

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90B

11

BA

575

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95B

11

BA

575

.010

369

B1

BA

576

.076

44B

1B

AA

577

.083

31B

C0

BA

577

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57B

1B

A5

78.0

1193

6L

1B

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80.0

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581

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96B

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85.0

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93.0

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373

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40.0

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31B

C0

BA

1042

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52.0

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1063

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64.0

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TA

ST

AS

IS -

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EE

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RV

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511

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BA

584

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511

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BA

585

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511

BP

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85.0

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546

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EA

SE

- S

PE

CIF

IC S

UR

VIV

AL

1221

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563

.512

241

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574

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65B

1B

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76.0

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587

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1B

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Sur

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Page A-17

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Tabl

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Com

plic

atio

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ata

for

circ

le g

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s


Page A-18

RA

DIC

AL

P

RO

ST

AT

EC

TO

MY

RA

DIA

TIO

N:

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Fig

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Page A-20

0.0

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Page A-21

Fig

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Page A-22

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Page A-24

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Page A-25

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Page B-1

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Page I-1

Index

AActual and actuarial data, use of, 10, 23–24Adenocarcinoma, 1, 12. See alsoProstate cancerAmerican Joint Committee (TNM) staging system, 1, 13, 14Androgen deprivation, 2, 15, 44

BBiochemical markers, 6, 44. See alsoProstate specific antigen

(PSA)Bladder neck contracture, 2, 21, 27, 31, 36, 38Bleeding (major), 2, 3, 21, 22, 27, 31, 36, 38, 39Brachytherapy. See alsoRadiotherapy

advantages and disadvantages of, 5, 39–40complications from, 5, 17, 27, 31, 40patient selection for, 5, 17–18, 38progression data for, 26, 34–35survival data for, 25, 28–30, 32techniques for, 18, 43as treatment alternative, 2, 5, 15, 38–40

CChemotherapy, 2, 15, 44Clinical staging. SeeStagingClinically localized prostate cancer. See alsoProstate cancer;

Stage T2 (B)background information for, 1–2, 12detection rate for, ilimitations of research on, 6, 9–10, 42–43recommendations for future research on, 6–7, 43–45

Colorectal cancer, 1, 12Complications. Seespecific complications; Treatment complica-

tionsComputerized tomography (CT) scans, 2, 14Cost factors, 22, 40, 45Cryotherapy, 2, 15, 43Cystitis, 2, 3, 5, 21, 22, 27, 31, 36, 38, 39

DDeath. SeeMortalityDiarrhea, 27, 36, 39Digital rectal examination (DRE)

clinical staging using, 2, 14detection using, imonitoring with, 20, 40

Disease-specific survival. SeeSurvival

EErectile dysfunction, 2, 3, 5, 21, 22, 27, 31, 36, 38, 39, 40External beam radiotherapy. See alsoRadiotherapy

advantages and disadvantages of, 5, 39complications from, 5, 17, 27, 35, 36, 39conformal therapy and, 7, 16, 44patient selection for, 5, 16–17, 38progression data for, 26, 34survival data for, 25, 28–30, 32, 33target volume and, 17technological improvements in, 7, 16, 44as treatment alternative, 2, 5, 15, 38, 39

GGleason grading system, 13

HHealth status, treatment selection based on, 4, 37

IImpotence. SeeErectile dysfunctionIncontinence. SeeUrinary incontinenceInterstitial radiotherapy. SeeBrachytherapy

JJewett-Whitmore (ABCD) staging system, 1, 13, 14

LLife expectancy, 21

estimation of, 19treatment selection based on, 4, 12–13, 16, 37

Lung cancer, 1, 12Lymph node dissection, 42. See alsoPelvic lymph node dissection

(PLND)Lymph nodes as target volume (radiotherapy), 16–17

MMagnetic resonance imaging (MRI), 2, 14Meta-analysis, definition of, 9Metastasis-free survival. SeeSurvivalMortality

from prostate cancer, i, 1, 4, 12, 37, 40, 41treatment related, 2, 3, 21, 22, 27, 31, 36, 38–39

NNational Institutes of Health (NIH), i

OOutcomes. SeeTreatment outcomesOverall survival. SeeSurvival

PPelvic lymph node dissection (PLND), 2, 14, 32, 42Proctitis, 5, 21, 27, 31, 35, 36, 39Progression, 3, 8, 21, 33, 40

analysis of data, 26, 34–35categories (local, distant, biochemical, total), definitions of, 24rates, 3, 21–22, 26, 34–35

Progression-free survival. SeeSurvivalProstate cancer. See alsoClinically localized prostate cancer; spe-

cific stagesbackground of, 1–2, 12detection of, igrowth rate of, 1, 12–13mortality from, i, 1, 4, 12, 37, 40, 41natural history of, 1, 12–13staging of, 1–2, 13–15

Prostate Cancer Clinical Guidelinesdata display for survival and disease progression and, 10data extraction for, 9data inadequacies and, 9–10


Page I-2

literature citations and panel opinions in discussion sections in,10–11

literature searches used in, 9methods and definitions of, 8–9treatment complications data and, 10

Prostate specific antigen (PSA)clinical staging using, 1, 2, 13, 14, 15, 44detection using, i, 14, 43, 44to determine recurrence, 3, 19, 24, 33, 43monitoring progression with, 20, 24, 33, 40, 45as predictor of pelvic lymph node metastases, 14–15

Prostatectomy. SeeRadical prostatectomyPsychological factors, 3, 21, 41Pulmonary embolism, 2, 21, 27, 31, 36, 39

QQuality of life, 7, 22, 41, 45

RRadiation cystitis, 2, 3, 5, 21, 22, 27, 31, 36, 38, 39Radical prostatectomy, 4, 38

advantages and disadvantages of, 5, 38–39complications from, 27, 31, 35, 36, 38–40definition of, 4, 38life expectancy and decision for, 16nerve-sparing techniques, 16, 39, 43overall survival rates for, 28patient age and, 3patient selection for, 15–16, 38performance of, 16, 43progression data for, 26, 34recommendations for research on, 7, 43, 44survival data for, 25, 28–29, 32, 33as treatment alternative, 2, 5, 15, 38–39

Radionuclide bone scan, 2, 15, 16Radiotherapy. See alsoBrachytherapy; External beam

radiotherapyadvantages and disadvantages of, 5, 39–40complications from, 5, 17, 27, 31, 35, 36, 39, 40definition of, 4, 38patient selection for, 5, 16–18, 38progression data for, 26, 34–35recommendations for research on, 7, 44survival data for, 25, 28–30, 32, 33as treatment alternative, 2, 5, 15, 38–40

Rectal injury, 2, 3, 21, 22, 27, 35, 36, 39Recurrence of disease, 3, 19, 21, 22, 24, 26, 33, 34, 40, 43. See

alsoProgression

SSeminal vesicles, 4, 16–18, 38Serum acid phosphatase, 2, 14, 15, 17, 24Spinal cord compression, 41Stage BO. SeeStage T1cStage M1 (D2), i, 35Stage T1 (A)

detection rate at, isurvival rate and, 2, 17treatment outcomes for, 2

Stage T2 (B)detection rate at, ilimitations in literature for, 6progression and, 34, 35review of literature on, 8, 9survival rate and, 2, 17, 33treatment complications of, 36

treatment outcomes for, 2, 23

Stage T2 (C), 17

Stage T1c, 1, 6, 14

Stage T3-T4 (C), i, 35, 37

Staging. See alsospecific stages

improvements needed, 1, 2, 7, 13, 44

methods used for, 1–2, 14–15

Standard patient, 6, 37

Stress urinary incontinence. SeeUrinary incontinence

Surveillance

advantages and disadvantages of, 5, 40–41

basis for management by, 18–19

patient selection for, 19, 38

progression data for, 26, 34

recommendations for research on, 7, 44

survival data for, 25, 28–31, 32, 33, 40

as treatment alternative, 2, 5, 15, 38, 40–41

Survival, 3, 8, 10, 21, 40

analysis of, 25, 32–33

categories (overall, progression free, metastasis free, diseasespecific), definitions of, 24

rates, 2, 3, 21, 25, 28–33

TThermotherapy, 2, 15

TNM staging system, 1, 13, 14

Toxicity from radiotherapy. SeeRadiotherapy, complications from

Transrectal ultrasonography (TRUS), 2, 14, 17, 39–40

Transurethral resection of the prostate (TURP), 17, 19, 40

Treatment complications, 2, 3, 5, 21, 22, 27, 31, 35–36, 38, 39, 40,41

outcomes data for, 10, 27, 31, 35–36

problems with data for, 10, 35

Treatment outcomes

analysis of summary tables of, 32–35

from available literature, 3, 22

tables and graphs summarizing, 22–32

types of, 2, 3, 21, 22

variability of data on, 9–10, 22, 32, 42–43

Treatment recommendations

alternatives, 5

levels of, 3, 6, 37

standards, 4, 37–38

Tumors. See alsoClinically localized prostate cancer

grading, 13

growth rate of, 1, 12–13

stage determination of, 1–2, 13–15

treatment selection based on characteristics of, 17, 37–38

UUrethral stricture, 2, 21, 27, 31, 36, 38

Urinary incontinence, 2, 3, 5, 21, 22, 27, 31, 35, 36, 38, 39, 40


American Urological Association, Inc.

This Report on the Management of Clinically Localized Prostate Cancerwas developed by theProstate Cancer Clinical Guidelines Panel of the American Urological Association, Inc.

This Report is intended to furnish to the skilled practitioner a consensus of clear principles andstrategies for quality patient care, based on current professional literature, clinical experience andexpert opinion. It does not establish a fixed set of rules or define the legal standard of care, pre-empting physician judgment in individual cases.

An attempt has been made to recommend a range of generally acceptable modalities of treat-ment, taking into account variations in resources and in patient needs and preferences. It is recom-mended that the practitioner articulate and document the basis for any significant deviation fromthese parameters.

Finally, it is recognized that conformance with these guidelines cannot ensure a successfulresult. The parameters should not stifle innovation, but will, themselves, be updated and willchange with both scientific knowledge and technological advances.

Board of Directors (1995 – 1996)

Practice Parameters, Guidelines and Standards Committee (1995 – 1996)

Health Policy Department Staff and Consultants

Charles F. McKiel, Jr., MD*Jack W. McAninch, MD*C. Eugene Carlton, Jr., MD*William R. Turner, Jr., MD*Roy J. Correa, Jr., MD*Harry C. Miller, Jr., MD*Dennis J. Card, MD*E. Darracott Vaughan, Jr., MD*Joseph C. Cerny, MD*

Gerald Sufrin, MD*Thomas P. Ball, Jr., MD*Lloyd H. Harrison, MD*Lawrence W. Jones, MD*Harry E. Lichtwardt, MDAbraham T. K. Cockett, MDH. Logan Holtgrewe, MDWinston K. Mebust, MDMartin I. Resnick, MD

Joseph N. Corriere, Jr., MDDavid M. Drylie, MDG. James GallagherRichard J. HanniganThomas D. Brockman Melanie H. Younger

*Voting member

Stephanie MenshDirector

Suzanne Boland PopeGuidelines Coordinator

Julie BowersAdministrative Assistant

Kim HagedornHealth Policy Projects Coordinator

Robin HudsonSecretary

Lisa EmmonsHealth Policy Manager

Tracy KielyHealth Policy Information Assistant

Betty RobertsHealth Policy Assistant

Megan CohenGovernment Relations Coordinator

Roger WoodsGovernment Relations Assistant

Randolph B. FenningerWashington Liaison

Justine GermannLegislative Associate

William GlitzPublic Relations Consultant

Karen CostanzoUniversity of Texas,Southwestern Medical School

Winston K. Mebust, MD, ChairJoseph W. Segura, MD, Vice-ChairReginald C. Bruskewitz, MDJack S. Elder, MDThomas C. Fenter, MDJohn B. Forrest, MD

Drogo K. Montague, MDGlenn M. Preminger, MDJoseph A. Smith, MDIan M. Thompson, Jr., MDCharles E. Hawtrey, MD, ConsultantJohn D. McConnell, MD, Consultant

Linda D. Shortliffe, MD, ConsultantEdward S. Tank, MD, ConsultantClaus G. Roehrborn, MD, FacilitatorRoy J. Correa, Jr., MD, Ex-officioCharles F. McKiel, Jr., MD, Ex-officioWilliam R. Turner, Jr., MD, Ex-officio


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