[CANCER RESEARCH 37, 2745-2751, August 1977]

gorical divisions but rather as horizontal “flows―with development in each of the categories proceeding from left toright (from more basic to more clinical information), theconcept of the programmatic framework is obtained (Chart3). There was a need to acquire as much “basic―information as we could about the different categorical flows, a factthat is indicated by having an area marked “base-line information―at the extreme left of the diagram. In this diagram,the “flow'‘from left to right also indicates an increasedamount of information, something which, it was hoped,would ultimately permit either more effective clinical management or prevention of bladder cancer so that its morbidity and mortality could be significantly reduced.

At the beginning of the planning activity, the NationalBladder Cancer Project consisted of a headquarters organization located at St. Vincent Hospital in Worcester, Mass.,staffed with a Project Director and an Assistant ProjectDirector, and a Working Cadre composed of 9 people whowere experts in basic or clinical aspects of research inbladder cancer. This group of people, togetherwith many consultants, was responsible for formulating theappropriate questions for which answers would be sought.It was hoped that the subsequent implementation of theresearch program would provide information to answersome of the questions or to permit reformulation ofquestions in a more relevant fashion. At the outset,however, questions followed the categorical lines that wereestablished by the organizational pattern of the NationalCancer Institute.

As a consequence, the Working Cadre was divided intothe 4 committees mentioned earlier with experts in thevarious disciplines relevant to etiology, diagnosis, experimental biology, and treatment. Each of these committees,in turn, established 2 or more subcommittees, such as asubcommittee on chemical carcinogenesis which was comprised of some half-dozen experts in this special field alone(Chart 4). Some 40 biomedical scientists, in addition tomembers of the Working Cadre, served on the subcommittees. The charge given to these committees and subcommittees was to identify and define those areas theythought appropriate for investigation under the aegis of theNational Bladder Cancer Project.

The problem in developing a truly integrated researchprogram within this structure became evident when each ofthe committees and their constituent subcommitteesbrought in their proposed research plans in the areas ofetiology, diagnosis, experimental biology, and treatment.There was great difficulty in putting the several reportstogether to develop a coordinated, interdisciplinaryresearch approach. Eventually, it was realized that the

2745

Program Genesis

In September 1971, a group of scientists accepted theresponsibility of planning and developing a coordinated,grant-supported national program of research on bladdercancer, the National Bladder Cancer Project. Ultimately, thegoal of the program was to reduce the morbidity and mortality associated with this disease. This was, as Dr. ThomasJ. King noted (1), to be a new approach in which activescientists in the field were to be given the opportunity toorganize and implement a national program aimed at thefull scope of problems of urinary bladder cancer and inwhich the direction, coordination, and day-to-day scientificadministration were to be carried out at a headquartersinstitution other than the National Cancer Institute. In addition, this program was to function within the framework ofthe overall grant-supported research activities of the National Cancer Institute, with its emphasis on retaining thepeer review system of awarding research grants. An initialeffort was made to develop this research program by utilizing as many of the basic disciplines as possible in theplanning and implementation phases. The intent was tofocus the scientific information, concepts, and viewpointsfrom the basic and clinical disciplines through the “lenses―(categories) of epidemiology, prevention, experimentalmodels, detection, diagnosis, therapy, and rehabilitation toresult in a multidisciplinary research effort on a commonproblem: bladder cancer (Chart 1).

The major categories of etiology (cause and prevention),cancer biology and diagnosis, and cancer treatment represented 3 divisions of the National Cancer Institute at thetime this program was started. In addition, the NationalCancer Institute had a Division of Cancer Research Resources and Centers, formerly known as Extramural Activities or Research Grants. More recently a 5th division, Cancer Control and Rehabilitation, was added (Chart 2). Despite the fact that the desired bladder cancer program wasto be comprehensive and would therefore cut across theorganizational structure of the National Cancer Institute,the frame of reference for such a program was neverthelessthat of the organizational pattern of the National CancerInstitute. Accordingly, planning committees entitled Etiology, Detection-Diagnosis, Treatment-Rehabilitation , andExperimental Biology were organized.

If one begins with the organizational pattern of the National Cancer Institute and visualizes it not as vertical, cate

Presented at the National Bladder Cancer Conference, November 28 toDecember 1, 1976, Miami Beach, Fla.

2 Presenter.

AUGUST 1977

Overview of the National Bladder Cancer Project andConference Objectives1

Gilbert H. FrledelI,2 Robert E. Greenfield, Arthur G. Hilgar, and Leon B. Ellwein

National Bladder Cancer Project, St. Vincent Hospital, Worcester, Massachusetts 01610

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

rEtiology(causeandprevent@@j[Diagnosis[@@@rlmentaI__Biology{

TreatmentIncreasingInformation

G. H. Friede// et al.

Physiology

Genetics

\i rology

1in inunology

Cytology

Pharmacology

Pathology

Biomet ry

I @rt.'v@nt i‘)fl

Experinwntal Mod&.,l@

@ t I.( I 14lIt

I)i@t@

Therapy

Common Interestplus

Capabilityin

Bladder CancerResearch

Chart 1. Multidisciplinary focus on bladder cancer research.

DIAGNOSIS

ETIOLOGY ch.m,coI Co@cwoq.n.&sv@oioqyEpid.m,o4oqy09@s@,

tfrology

@ Working@ EXPERIMENTAL

I BsocP'sr'ss@@yL2th―

@ Cadre BIOLOGY@ °@@ Cuftw

rEIN,,@ P0thO@O5@-@T Eu'oaoq,

I Ms@c@ O,,coloqy

Chart 4. National Bladder Cancer Project original development of research plan.

I- SC0

0

E0

C

VC

VU,0

Chart 5. “Ninedot―puzzle.

one of the puzzles sometimes given to those attempting todeal with Gestalt psychology. The 9 dots illustrated in Chart5 are to be connected by 4 continuous lines. More oftenthan not the prospective problem solver begins in the upperleft hand corner and moves his pencil to the upper righthand corner and then down either diagonally to the lowerleft or vertically to the lower right. After these 2 moves, it isimpossible to meet the terms of the problem. The selfimposed limiting factor is the concept in the mind of theproblem solver that none of the lines may go beyond theimplicit boundaries of the 9-dot figure.

Chart 3. National Bladder Cancer Project original concept of research

difficulty lay in the way the problem had been defined.Several separate, although related, research programsexisted instead of a single coordinated program involvingmany disciplines. Truly multidisciplinary planning seemedto be inhibited by the conceptual framework provided bythe pattern of organized medical research exemplified bythe National Cancer Institute: 3 parallel divisions withoutobvious interlocking relationships.

The constricting effect of a preexisting and fairly rigidframe of reference in problem solving is well illustrated in

CANCER RESEARCH VOL. 372746

INTERDISCIPLiNARY FOCUS ON BLADDER CANCER RESEARCH

Bioc hem istry

Radiobiology

Clinical Medicine

Public Health I

l@.I r-:i

rj;iri-:ir;iI. Ilu II@ I @:@I@ a.—@I E I I . CIv) I •I t@@l@ [.:_@i@ LiiI.@°IIoI

c@'@ r ‘@ I@@l

LiiI :I. I

Etiology Biology R@ CRR.C ControlD5 (Grants)

Chart 2. Organizational divisions of the National Cancer Institute.

plan.

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

Overview and Objectives

additional lesions in the bladder. At the right ofthe diagram,intervention might take the form of surgery or radiotherapy.Thus, some form of intervention would be appropriate ineach phase of bladder cancer. Before interveningeffectively, however, it is necessary to develop an effectivemeans of classifying patients for treatment. This is ofparticular importance when a tumor is already present inthe bladder and the patient presents himself for treatment.

The question in practical clinical terms might be, ‘‘Givenan individual who enters the office of the urologist with abladder tumor, how can the urologist accurately assess theprognosis of that lesion in that patient so that the mostappropriate form of therapy can be instituted?―

In an attempt to provide an answer for the urologist andthe patient, a major consideration in the National BladderCancer Project research program has become theclassification of the tumor (and patient) for therapy. Asshown in Chart 7, this category is immediately adjacent to“Detectionand Diagnosis, ‘â€and information developedfrom studies in the latter category will be used in developingthe overall classification scheme and in the categorizationof individual patients. Yet, the development of theclassification has been, and continues to be, a complexmatter requiring input from basic and clinical scientistsfrom many disciplines. Moreover, the various disciplinaryapproaches must be applied concurrently and notconsecutively. In order to determine which features of thetumor will make that lesion susceptible to a particular formof treatment, those considering the matter must beknowledgeable about the therapeutic procedures themselves and the range of results that might be expected fromutilization of the therapy regimen. Whether or not a particular tumor and patient are candidates for radiation therapy requires not only knowledge of the various therapeuticprocedures that might be used but also some knowledge ofthe various kinds of tumors against which this modalityis the most effective.

In the past, morphology was the major means of classifying tumors. Today, however, pathologists are recognizingto a greater extent not only different patterns of tumorgrowth but also tissue manifestations of the interaction between the tumor and the host. When possible, this information is being used in the selection of the most appropriatetreatment. Within the National Bladder Cancer Project,every effort is being made to broaden the basis of classification of tumors. Pathological studies will undoubtedly continue to yield information about the biology of tumors andtheir hosts, but other means are also being used to studythe characteristics of bladder tumors. Moreover, manyapproaches are being taken to assess the response, or thepotential response, of the host to both his tumor and thetreatment.

Again, although we are focusing attention on the courseof the disease in patients, care has been taken to assure thatthe basic scientist is not left out of either the planning or theresearch effort. On the contrary, both basic and clinicalscientists have been involved in research planning from theinception of the program. Basic scientists have been willingto learn something about the clinical aspects of bladdercancer because this information becomes essential to themin the interpretation of their experimental data derived from

Chart 6. Solution to “ninedot―puzzle.

If, however, one accepts the terms in the problem literallyand is not restricted by a self-imposed concept ofboundaries, it is possible to solve the problem as illustratedin Chart 6. If the initial line is carried beyond the corner doton the upper right a distance equal to the distance between2 dots, and then is drawn diagonally down to the left goingthrough the indicated dots, the problem is readily solved.Whether or not a solution is reached depends on the frameof reference of the solver. The restrictions one acceptswhen framing the question may well determine whether ornot one can come up with an answer.

Disciplinary Integration

. The challenge to the Working Cadre was to view the

bladder cancer problem without preconceived disciplinaryconstraints, but it was not until it had begun to acquireinformation through implementation of the originalresearch plan that the Working Cadre found that the mosteffective way to integrate the basic and clinical informationgenerated within the program was to focus on the course(s)of the disease(s). Sequential stages were hypothesized,beginning with the normal individual who, for one reasonor another, enters a high-risk category. The sequence continues through the development of epithelial changes inthe bladder that might be called preneoplastic, to “early―superficial bladder cancer lesions that can “recur―afterremoval or other treatment, following which locally invasivedisease, regional disease, and, ultimately, metastases anddeath of the patient may occur. When attention wasdirected in this way to the course of the disease rather thanto categorical approaches to it, the development ofresearch questions, including those dealing with etiology,diagnosis, and therapeutic intervention, was far easier.

It became apparent that therapy, or intervention, mustconstantly be considered in the light of a progressing orchanging disease status, reflecting the dynamics of thedisease process. In Chart 7, the progressively less favorableoutlook for the patient, depicted by the “fallingman,―issuperimposed on the phases through which bladder cancerpatients pass. It would be desirable to have a means ofintervening in all phases of the “declineand fall,―tailoringthe intervention to the phase of the disease. If, at the far leftof the diagram, we could intervene and remove thecarcinogenic agent from the environment or possibly alterthe response of the individual to the carcinogenicsubstance, we might prevent the development of bladdercancer. Moving toward the center of the diagram, if wecould identify promoting agents, perhaps we could removethem or neutralize them and thus prevent the appearance of

AUGUST1977 2747

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

G. H. Friedell et al.

Chart 7. National Bladder Cancer Project concept of interdisciplinary research focusing on the course of the disease.

studying human tumor tissue. It is not enough for a basicscientist to know that he is working with tumor tissue; heneeds to know what proportion of the tissue is stroma andwhat proportion is the epithelial component. He needs toknow something about the ‘‘degreeof malignancy' ‘of thetumor, and he would like to know something about thesubsequent course of the patient. All of this informationmust be obtained by the clinician during management andfollow-up of the patient. Conversely, the clinician begins tounderstand the language of the basic scientist, becomesfamiliar with the outlines of some experimental procedures,and becomes aware of the difficulties of some areas ofresearch: for example, the difficulties of establishing celllines from human bladder tumors or from human bladderepithelium.

It is no small achievement that the clinicians involved thusfar in the program of the National Bladder Cancer Projectbecame concerned about the size, or even the existence, ofappropriate control groups when the discussions turned toclinical as well as experimental studies. It was equallyimpressive to us that the basic scientists involved in thereview process wanted to know whether there wereappropriate assurances from clinicians collaborating in thegrant application, not only that there would be a urologistproviding material, but that he would be an activeparticipant in the study with the responsibility to provideinformation about the patient both at the time the specimenwas obtained and over an appropriate follow-up period.

This awareness of bladder cancer as a disease spectrum,during the course of which there must be constantreevaluation of information from the patient in order to keepcurrent the classification of the patient for therapy, isreflected in Chart 7. By focusing on the changing nature ofthe disease, it has been possible to have both basic andclinical scientists begin to think a bit more as the other onewould. This in turn has facilitated progress toward the goalof a concerted multidisciplinary research program.

One of the results of the integration of basic scientistswith clinical scientists has been the disappearance, at leastfrom the organizational diagrams, of the “experimentalbiology―research flow evident in Chart 3. Initially, ‘‘experimental biology―included the study and development ofexperimental models to elucidate the pathogenesis ofbladder cancer and its behavior in a variety of experimentalcircumstances. As considerations of basic research mergedwith those of clinical research, experimental biology became less a separable group of experimental techniquesand began to be thought of in conjunction with clinicalstudies in the broad categories of etiology, detection anddiagnosis, classification of patients for therapy, or treatment. When the research budget of the National BladderCancer Project for fiscal year 1975 was reviewed, it wasfound that the program was divided approximately in thirdsbetween cause and prevention, detection and diagnosisand classification of patients for treatment, and treatmentand rehabilitation.

2748 CANCERRESEARCHVOL. 37

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

Overview and Objectives

The treatment segment of the program has developedslowly because it became clear only after intensive planningthat the kind of research that should be done could not befocused exclusively on comparing one modality oftreatment with another or testing one therapeutic agentagainst another, i.e., the use of specific treatmentprotocols. Unless additional information about the courseof the disease in various patient populations underaccepted treatment could be obtained, application of theresults of broad randomized trials to decisions on specificsubpopulations might be not only inappropriate butalso misleading. Although much has been written on thesubject, hard data were in short supply when the projectwas initiated. Indeed, the very nature of bladder cancerprecludes a study of the true “naturalhistory. “Theurologist often sees the patient first when the only visiblemanifestation of disease during cystoscopy is a smallsuperficial papillary lesion. Becausethis lesion is frequentlyremoved in its entirety as a diagnostic biopsy, the diagnostic procedure often doubles as the therapeutic procedure. What is required is information about the history ofthis disease as it is continually being modified by intervention of one sort or another, i.e., the “unnaturalhistory.―

In Chart 8, an attempt has been made to illustrate graphically the interaction of basic and clinical research as onefocuses on the course of clinical disease. A 3-dimensionalapproach has been used to illustrate the course of thedisease from left to right, the interaction between clinicalstudies at the front, and basic research at the back. Research workers on any vertical plane of the diagram can be

focused on the same particular aspect of the bladder cancerproblem as is illustrated on the front section. For example,both clinical and basic research investigators can be focusing on the classification of “early―lesions in the bladderand the host bearing these lesions. A reference to thisdiagram is perhaps the best means of recognizing that theimportance of the multidisciplinary group is not merely toprovide a multifaceted answer to a preset question, but,more importantly, to formulate the correct question. Thisapproach also permits the incorporation of both basic andclinical scientists in a continuing program of data reviewfrom which new questions can be formulated or originalones modified.

Program Accomplishments

The fact that the National Bladder Cancer Project represents an integrated multidisciplinary approach to the human bladder cancer problem is an achievement in itself.The project is addressing the broad spectrum of concernsrelated to cancer of a specific site with a coordinated research program running the gamut from etiology to rehabilitation through investigator-initiated research grants processed through the peer review mechanism. To date, somespecific and readily recognizable advances can be attributed to the existence of the Project. Many of these arediscussed in the papers presented at this conference. Examples of general progress made include the following.

First of all, the concept of multidisciplinary clinical management of patients with bladder cancer has been furthered

Chart 8. Three-dimensional illustration of basic and clinical research interaction.

AUGUST1977 2749

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

G. H. Friedell et a!.

significantly in many institutions by the development ofinvestigations under the aegis of the National Bladder Cancer Project. Some of these investigations have been carriedon within individual institutions, whereas others are beingcarried out by a collaborating group of investigators basedin several different institutions. Moreover, in several ofthese institutions there has been increased involvement ofbasic scientists in thinking about clinical problems relatedto bladder cancer. The multidisciplinary approach to classifying patients and their tumors for therapy is encouragingmovement away from the concept of sequential management, in which one physician does what he thinks is appropriate and then passes the patient on to another physicianusing a different therapeutic modality. Sequential patientmanagement is giving way to consultation among urologists, pathologists, radiation oncologists, and medical oncologists before definitive therapy is undertaken. Thisseems to be occurring particularly in those institutions inwhich urologists have become involved with, or are awareof, the activities of the National Bladder Cancer Project.

A 2nd advance, also concerned with clinical managementof patients with bladder cancer, is the increasing use ofcytological studies and of selected-site mucosal biopsies todetermine the presence and extent of neoplastic changes inbladder epithelium both at the time of the original diagnosisand in patient follow-up. In part, as a result of the activitiesof the National Bladder Cancer Project, urologists are becoming increasingly aware of the need to assess the malignant potential of the bladder epithelium that is not removedand of our capability to do so.

The organization of groups of collaborating or cooperating institutions to conduct clinical studies comparing different therapeutic modalities or to study chemotherapy formanifest systemic disease or as an adjuvant before systemicdisease becomes evident might also be considered as advances for which the National Bladder Cancer Project cantake credit.

In the area of etiology, new methodology has been developed for identifying trace amounts of known chemical carcinogens. With these tools it may be possible to identifyhigh-risk environments or to identify individuals who havebeen exposed to even low doses of known carcinogenicchemicals. Studies of experimental models have also beensupported to provide additional information about etiological factors in bladder cancer.

Such models might be defined as experimental systems,in vitro or in vivo, in which we can study some aspect ofhuman disease that cannot be studied directly in humanpatients or in experimental subjects. One must realize, ofcourse, that experimental models, at least experimentalanimal models, are of several different kinds. One modelthat might be used for screening potentially carcinogenicchemical compounds could be the animal itself. Dependingon various factors, the investigator would make a decisionas to whether to use a dog, rat, hamster, or some otheranimal for this purpose, but the animal itself would be themodel. Alternatively, an investigator might use an experimental animal model for studying the induction and pathogenesis of bladder cancer, in which case the tumor and theanimal together would comprise the model.

In another example, an investigator might wish to use an

experimental model for studying the biology or the naturalhistory of bladder cancer. One might wish to focus evenmore specifically on patterns of spread and metastatic disease. In the latter case, one might utilize a primary tumoranimal system in which metastasis from an induced primarytumor was frequent and highly predictable, a tumor-animalsystem with systemic inoculation of a transplantable tumor,or the local inoculation of a serially transplantable tumor inan inbred strain of animal. Such animal models, and 0thers, in fact, have been developed for studying new techniques for the detection and diagnosis of bladder cancer orthe recurrence of local disease, for investigating intravesiCal chemotherapy for local disease, or for investigatingchemotherapeutic agents to be given systemically for metastatic bladder cancer.

Later in the conference you will be hearing about some ofthese experimental models, but here 2 particular modelswill be cited. In the general area of bladder cancer detection, the application of scanning electron microscopy to thestudy of exfoliated bladder epithelial cells has made it possible, in experimental models at least, to detect the presence of an irreversible change in the bladder epitheliumafter only 10 weeks of carcinogen administration, whereasby standard light microscopic techniques of examining exfoliated cells, the diagnostic criteria for malignancy are notmet until 60 weeks have elapsed. Comparable studies havenow been inaugurated in patients with bladder tumors. Inthe general area of therapy, one of the animal models hasbeen particularly useful in allowing us to select potentiallyeffective single and combination chemotherapeutic agentsfor either locally recurrent or metastatic bladder cancer.From 1 of these models came the suggestion that cis-diamminedichloroplatinum(ll) might be effective in treating advancedhuman bladdercancer.

Finally, it is hoped that all will agree at the end of thisconference that a meeting of this kind, focused on bladdercancer research, will itself be considered as something ofan advance. If bladder cancer research continues to expand, and if the National Bladder Cancer Project can continue to foster communication among the basic and clinicalresearch workers in the field, then it would seem desirableto have additional conferences of this type every 2 or 3years. In the intervening years, smaller workshops and symposia will be sponsored to consider more specialized topics.

In this conference, the chairman and the speakers in eachsession have been asked to focus on current knowledge:the state of the art, and then to indicate possible areas ofresearch that might be pursued. The Cochairman at the endof each session has been asked to outline further areas ofresearch and, where possible, to pinpoint programmaticneeds that have arisen as the National Bladder CancerProjecthasdeveloped.

In Session A, the papers will be concerned withdiagnosis, classification, and treatment of “patientswithregional and metastatic disease, and locally extensivedisease.―In this area, we have the most information aboutbladder cancer, but at the same time, we can do the least forthepatient.

Session B will be concerned with early disease, detectionand diagnosis, and with both human and experimental

2750 CANCERRESEARCHVOL. 37

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

Overview and Objectives

studies on the pathogenesis of bladder cancer.Session C will deal primarily with classification of the

tumor and host for therapy. It should provide both theclinician and basic research worker with informationconcerning the spectrum of disease in a high-risk individualif that individual has local invasive disease. Papers in thissession should give a fairly good idea of the approachesthat many research workers are taking in an attempt toprovide information for the clinician regarding patientmanagement.

In Session D, the management of superficially invasivebladder cancer will be discussed. The importance ofassessing the neoplastic potential of residual bladderepithelium will be stressed, and both clinical andexperimental studies of the management of “recurrent―disease will be highlighted. The possibility of intervening inthe course of the disease in order to prevent “recurrence―will be noted as well as means of treating already evidentcancer.

Session E will deal with the cause and prevention ofbladder cancer, the area where the least new information isavailable. This last point is somewhat ironic, since theinformation that we did have about bladder cancer severalyears ago, the fact that bladder cancer was a consequenceof exposure of workers in some industriesto certainchemicals, was probably one of the reasons leading to the

establishment of the National Bladder Cancer Project. Thatis, it seemed as though for at least 1 cancer we had someinformation about etiology, and consequently it was hopedthat meaningful steps could be taken toward prevention.

Finally, as a preface to some of the remarks that Dr. VictorF. Marshall will make later in the conference (2), thedevelopment of the National Bladder Cancer Project wasdue in large measure to the efforts of Dr. Rubin Flocks. Dr.Flocks recognized several years ago that we were in theposition occupied by Session A on this program. A fairamount was known about bladder cancer in its moreadvanced stages, and yet very little could be done about thedisease in that stage. The only way to increase ourcapability to intervene effectively at earlier, more promisingstages of disease (toward the left side of Chart 8) was todevelop a research program combining both basic andclinical research. If this conference is helpful to you and ifthe National Bladder Cancer Project meets even some ofyour expectations, then we all owe a debt of gratitude toDr. Flocks.

References

1. King, T. J. The Organ Site Programs and the National Cancer Program.cancerRes.,37:2743-2744,1977.

2. Marshall, V. F., and McCarron, J. P., Jr. The Curability of Vesical Cancer:Greater Now or Then? Cancer Res., 37: 2753-2755, 1977.

AUGUST 1977 2751

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from

1977;37:2745-2751. Cancer Res   Gilbert H. Friedell, Robert E. Greenfield, Arthur G. Hilgar, et al.   Conference ObjectivesOverview of the National Bladder Cancer Project and

  Updated version

  http://cancerres.aacrjournals.org/content/37/8_Part_2/2745.citation

Access the most recent version of this article at:

   

   

   

  E-mail alerts related to this article or journal.Sign up to receive free email-alerts

  Subscriptions

Reprints and

  .pubs@aacr.orgDepartment at

To order reprints of this article or to subscribe to the journal, contact the AACR Publications

  Permissions

  Rightslink site. Click on "Request Permissions" which will take you to the Copyright Clearance Center's (CCC)

.http://cancerres.aacrjournals.org/content/37/8_Part_2/2745.citationTo request permission to re-use all or part of this article, use this link

Research. on August 23, 2021. © 1977 American Association for Cancercancerres.aacrjournals.org Downloaded from