Cancer Survivorship Prostate Cancer Risks and Treatments © 2005 University of California Regents Cancer Survivorship Grant Start Case Photo collection

Cancer SurvivorshipProstate Cancer Risks and Treatments

© 2005 University of California RegentsCancer Survivorship Grant

StartCase

Photo collection is courtesy of PEIR - University of Alabama at Birmingham Department of

Pathology via the HEAL (Health Education Asset Library) database

Goal of this Module

This is an interactive and self-directed learning module This is an interactive and self-directed learning module intended to build a foundation of knowledge around the intended to build a foundation of knowledge around the epidemiology and late effects of cancer survival. This is epidemiology and late effects of cancer survival. This is one of several educational modules you will complete one of several educational modules you will complete during your core clinical clerkships. Themes during your core clinical clerkships. Themes emphasized in this, and other modules, are:emphasized in this, and other modules, are:

Epidemiology of survivalEpidemiology of survival Late effectsLate effects Psychosocial concernsPsychosocial concerns Secondary preventionSecondary prevention Strategies for behavior changeStrategies for behavior change

Meetyour

patient

Paul R. State III is a 55-year old African-American Paul R. State III is a 55-year old African-American male who presents to a family practice clinic because male who presents to a family practice clinic because his wife insists he have a prostate evaluation. He is in his wife insists he have a prostate evaluation. He is in good health and has no active medical issues or good health and has no active medical issues or symptoms. He has not seen a doctor in over 5 years, symptoms. He has not seen a doctor in over 5 years, but his 51-year old brother was recently diagnosed but his 51-year old brother was recently diagnosed with prostate cancer and Mr. State’s wife insisted that with prostate cancer and Mr. State’s wife insisted that he be evaluated for prostate cancer, as well. He had a he be evaluated for prostate cancer, as well. He had a prostate-specific antigen (PSA) test done a few weeks prostate-specific antigen (PSA) test done a few weeks ago, and Mrs. State says you should have the results in ago, and Mrs. State says you should have the results in the computer. He reports no obstructive symptoms of the computer. He reports no obstructive symptoms of hesitancy, incomplete emptying, double voiding, or hesitancy, incomplete emptying, double voiding, or dribbling. He has no irritative symptoms of urgency, dribbling. He has no irritative symptoms of urgency, frequency, or nocturia. frequency, or nocturia.

Case continued

Case continued

Family history is significant only for his brother who was Family history is significant only for his brother who was recently diagnosed with prostate cancer. He has smoked recently diagnosed with prostate cancer. He has smoked 2 packs of cigarettes a day since he was 20 years old, 2 packs of cigarettes a day since he was 20 years old, drinks 1-2 beers per day, and denies using drugs. He drinks 1-2 beers per day, and denies using drugs. He works as a manager at a local car garage. He eats fast works as a manager at a local car garage. He eats fast food daily because he can’t resist double doubles from food daily because he can’t resist double doubles from In-N-Out next to his shop.In-N-Out next to his shop.

His wife leaves the room for the physical exam. As soon His wife leaves the room for the physical exam. As soon as she leaves, he says “I’m not really at risk for prostate as she leaves, he says “I’m not really at risk for prostate cancer, right doc? I just want my wife to get off my cancer, right doc? I just want my wife to get off my back.”back.”

Go to Question #1

Question #1: Which of Mr. State’s risk factors poses the largest relative risk for prostate cancer?

A.A. EthnicityEthnicity

B.B. AgeAge

C.C. Family HistoryFamily History

D.D. DietDiet

E.E. Environmental ExposureEnvironmental Exposure

Question #1: Incorrect Answer

A.A. Ethnicity: African-Americans are at higher risk Ethnicity: African-Americans are at higher risk for prostate cancer than matched Caucasians. On for prostate cancer than matched Caucasians. On average, they present with more advanced average, they present with more advanced disease at initial diagnosis. The potential disease at initial diagnosis. The potential increased mortality for African-Americans increased mortality for African-Americans compared to Caucasians is controversial. compared to Caucasians is controversial. Prostate cancer screening should begin at 40 Prostate cancer screening should begin at 40 years of age for African-Americans. Ethnicity years of age for African-Americans. Ethnicity does not pose the largest relative risk in this does not pose the largest relative risk in this patient.patient.

Return to Question #1Ethnicity article (Kang, BJU 2004)

Question #1: Correct Answer

B.B. Age: The incidence of prostate cancer Age: The incidence of prostate cancer increases with age. Clinically significant increases with age. Clinically significant prostate cancer develops in 0.01% of prostate cancer develops in 0.01% of men<40 years old, 1% of men 40-59 years men<40 years old, 1% of men 40-59 years old, and 13% of men over the age of 60. old, and 13% of men over the age of 60.

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Age article (Thompson, NEJM 2004)

Question #1: Incorrect AnswerC. Family History: The age at which the disease C. Family History: The age at which the disease

was diagnosed in a first-degree family member was diagnosed in a first-degree family member is vital to determining the relative risk for Mr. is vital to determining the relative risk for Mr. State. The relative risk for prostate cancer is 4-State. The relative risk for prostate cancer is 4-7x if the age of onset was 50 years old, 3-5x if 7x if the age of onset was 50 years old, 3-5x if the age of onset was 60 years old, and 2-4x if the the age of onset was 60 years old, and 2-4x if the age of onset was 70 years old. Prostate cancer age of onset was 70 years old. Prostate cancer screening should begin at 40 years of age for screening should begin at 40 years of age for patients with a family history of prostate cancer.patients with a family history of prostate cancer.

Return to Question #1

Family history article (Thompson, NEJM 2004)


D. Diet: Although high fat intake doubles D. Diet: Although high fat intake doubles Mr. States risk of prostate cancer, diet Mr. States risk of prostate cancer, diet does not pose the largest relative risk.does not pose the largest relative risk.


Diet article (Mazhar: BJU 2004)


E. Environmental exposure: His risk of E. Environmental exposure: His risk of prostate cancer increases with exposure to prostate cancer increases with exposure to alkaline batteries, welding chemicals, and, alkaline batteries, welding chemicals, and, possibly, tobacco (all contain cadmium, possibly, tobacco (all contain cadmium, which is carcinogenic in the prostate.) which is carcinogenic in the prostate.) However, these exposures do not pose the However, these exposures do not pose the largest relative risk.largest relative risk.


Environmental exposure article (Deutsch: Lancet Oncol 2004)

Case Continued

On physical exam, Mr. State is obese and in On physical exam, Mr. State is obese and in no apparent distress. HEENT, no apparent distress. HEENT, cardiovascular, pulmonary, and abdominal cardiovascular, pulmonary, and abdominal exams are within normal limits. exams are within normal limits.

Continuecase

Case Continued

On rectal exam, sphincter tone is normal. On rectal exam, sphincter tone is normal. The prostate margins are distinct and it The prostate margins are distinct and it appears to be normal in size, but a firm, 0.5 appears to be normal in size, but a firm, 0.5 cm x 0.5 cm nodule is palpated along the cm x 0.5 cm nodule is palpated along the right lateral sulcus.right lateral sulcus.

After the exam, you remember to check Mr. After the exam, you remember to check Mr. State’s labs on the computer. CBC and State’s labs on the computer. CBC and Chem-7 are within normal limits. PSA is 4.8.Chem-7 are within normal limits. PSA is 4.8.

Go to Question #2

Question #2: Which of the following factors will allow you to decide definitively whether Mr. State has prostate cancer?

A.A. PSA velocityPSA velocity

B.B. Age-adjusted PSAAge-adjusted PSA

C.C. PSA densityPSA density

D.D. Ratio of free PSA to bound PSARatio of free PSA to bound PSA

E.E. None of the aboveNone of the above


A.A. PSA velocity: A change in PSA (PSA PSA velocity: A change in PSA (PSA velocity) of >1.5 ng/mL over 2 years may velocity) of >1.5 ng/mL over 2 years may be associated with prostate cancer. be associated with prostate cancer. However, the same laboratory should be However, the same laboratory should be used, and even then PSA velocity has a low used, and even then PSA velocity has a low sensitivity and specificity for prostate sensitivity and specificity for prostate cancer.cancer.


PSA velocity article (D’ Amico: NEJM 2004)


B.B. Age-adjusted PSA: Adjusting PSA for Age-adjusted PSA: Adjusting PSA for age increases the sensitivity for younger age increases the sensitivity for younger men and specificity for older men. The men and specificity for older men. The normal range, in ng/mL, is 0-2.5 for 40-49 normal range, in ng/mL, is 0-2.5 for 40-49 year olds, 0-3.5 for 50-59 year olds, 0-4.5 year olds, 0-3.5 for 50-59 year olds, 0-4.5 for 60-69 year olds, and 0-6.5 for 70-79 for 60-69 year olds, and 0-6.5 for 70-79 year olds. However, PSA is useful only as year olds. However, PSA is useful only as a screening tool, not for definitive a screening tool, not for definitive diagnosis.diagnosis.

Return toQuestion #2

Age-adjusted PSA article (Chu, Cancer 2002)


C.C. PSA density: The PSA density adjusts for PSA density: The PSA density adjusts for benign prostatic hyperplasia (BPH), since benign prostatic hyperplasia (BPH), since 1 gram of BPH tissue elevates PSA by 1 gram of BPH tissue elevates PSA by approximately 0.12 ng/mL. While a PSA approximately 0.12 ng/mL. While a PSA density >0.15 is more likely to warrant a density >0.15 is more likely to warrant a biopsy, it only raises the positive biopsy, it only raises the positive predictive value to 30-40%.predictive value to 30-40%.


PSA density (D’Amico: NEJM 2004)


D.D. Ratio of free PSA to bound PSA: Ratio of free PSA to bound PSA: Normally, approximately 90% of PSA is Normally, approximately 90% of PSA is bound to alpha-1-antichymotrypsin. Free bound to alpha-1-antichymotrypsin. Free PSA levels below 21% tend to correlate PSA levels below 21% tend to correlate with prostate cancer, while levels above with prostate cancer, while levels above 21% are often seen in older men whose 21% are often seen in older men whose disease is slowly progressing. These ratios, disease is slowly progressing. These ratios, however, must be correlated with other however, must be correlated with other studies.studies.


Ratio of free PSA to bound PSA article(Uemura: Int J Urol 2004)


E.E. None of the above: PSA>4ng/mL has a positive None of the above: PSA>4ng/mL has a positive predictive value of 20-30% for carcinoma of the predictive value of 20-30% for carcinoma of the prostate. While each of the above adjustments is prostate. While each of the above adjustments is useful in improving the sensitivity and specificity useful in improving the sensitivity and specificity of the test to some extent, PSA should still be used of the test to some extent, PSA should still be used to guide a further work-up and should be to guide a further work-up and should be considered in the context of the patient’s other considered in the context of the patient’s other personal risk factors, history, physical exam, and personal risk factors, history, physical exam, and other findings. PSA may be elevated secondary to other findings. PSA may be elevated secondary to BPH, urethral instrumentation, infection, prostatic BPH, urethral instrumentation, infection, prostatic infarction, or prostatic massage. The only way to infarction, or prostatic massage. The only way to definitively diagnose prostate cancer is with definitively diagnose prostate cancer is with biopsy.biopsy.

Continue case

Case Continued

You tell Mr. State that you would like to perform a You tell Mr. State that you would like to perform a trans-rectal ultrasound (trans-rectal ultrasound (TRUSTRUS)-guided biopsy. He )-guided biopsy. He argues that it is an uncomfortable procedure and says argues that it is an uncomfortable procedure and says he doesn’t see the point, but Mrs. State chides him he doesn’t see the point, but Mrs. State chides him that “the doctor knows best”. He agrees to the that “the doctor knows best”. He agrees to the procedure.procedure.

Before performing the TRUS, you try to predict Before performing the TRUS, you try to predict where a potential cancer might be found.where a potential cancer might be found.

Go to Question #3

TRUS-Guided Bx

Back tocase

The most common adverse event of prostate biopsy is rectal bleeding, which occurs in up to 50% of patients but rarely needs to be packed for tamponade. The most common minor complication is prostatitis, which occurs in approximately 2.5% of patients. Infectious complications requiring hospitalization are seen in <1% of patients who are properly medicated with antibiotics before biopsy.

Question #3: In which zone of the prostate will carcinoma most likely arise?

A.A. Transition zoneTransition zone

B.B. Peripheral zonePeripheral zone

C.C. Central zoneCentral zone

D.D. Anterior Anterior fibromuscularfibromuscular area area


A.A. Transition zone: 10-20% of prostatic Transition zone: 10-20% of prostatic carcinoma arises in the transition zone. carcinoma arises in the transition zone. Benign prostatic hyperplasia almost always Benign prostatic hyperplasia almost always occurs in the transition zone.occurs in the transition zone.



B.B. Peripheral zone: 65-70% of prostatic Peripheral zone: 65-70% of prostatic carcinoma arises in the peripheral zone. The carcinoma arises in the peripheral zone. The peripheral zone can be palpated on digital peripheral zone can be palpated on digital rectal exam (DRE), making DRE a useful rectal exam (DRE), making DRE a useful screening tool for prostate cancer.screening tool for prostate cancer.

Continue case


C.C. Central zone: About 5% of prostate cancer Central zone: About 5% of prostate cancer arises in the central zone.arises in the central zone.



D. Anterior fibromuscular area: Prostatic cancer D. Anterior fibromuscular area: Prostatic cancer rarely arises in the anterior fibromuscular rarely arises in the anterior fibromuscular area.area.


Case Continued

After pre-medication with broad-spectrum After pre-medication with broad-spectrum antibiotics, TRUS is performed and shows a antibiotics, TRUS is performed and shows a hypoechoichypoechoic pattern in the peripheral zone and the left pattern in the peripheral zone and the left base. Core biopsies of the base. Core biopsies of the hypoechoichypoechoic area are taken area are taken and random sampling is done by and random sampling is done by dodecaddodecad biopsies biopsies..

You go to the pathology lab to review the findings so You go to the pathology lab to review the findings so you can sound smart if your attending questions you. you can sound smart if your attending questions you. To your dismay, the pathologist asks you a series of To your dismay, the pathologist asks you a series of questions before reviewing the slides with you.questions before reviewing the slides with you.

Go to Question #4

Question #4: If Mr. State has cancer of the prostate, which is the most likely histology?

A.A. Small cell carcinomaSmall cell carcinoma

B.B. SarcomaSarcoma

C.C. AdenocarcinomaAdenocarcinoma

D.D. Transitional cell carcinomaTransitional cell carcinoma


A.A. Small cell carcinoma: Small cell Small cell carcinoma: Small cell carcinomas account for less than 1% of carcinomas account for less than 1% of prostate cancer.prostate cancer.



B.B. Sarcoma: Sarcomas account for less than Sarcoma: Sarcomas account for less than 1% of prostate cancer.1% of prostate cancer.



C.C. Adenocarcinoma: Adenocarcinomas account for over Adenocarcinoma: Adenocarcinomas account for over 95% of prostate cancers. The distinguishing histologic 95% of prostate cancers. The distinguishing histologic characteristic of prostate cancer is the absence of basal characteristic of prostate cancer is the absence of basal cells, which can be seen with high-molecular-weight cells, which can be seen with high-molecular-weight keratin staining (which stains basal cells). Absence of keratin staining (which stains basal cells). Absence of staining is consistent with carcinoma of the prostate. staining is consistent with carcinoma of the prostate.

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D.D. Transitional cell carcinoma: Transitional Transitional cell carcinoma: Transitional cell carcinomas account for approximately cell carcinomas account for approximately 4% of prostate cancer. They do account 4% of prostate cancer. They do account for over 90% of bladder cancer.for over 90% of bladder cancer.


Case ContinuedUpon viewing the slides with the pathologist, you Upon viewing the slides with the pathologist, you note a basophilic cytoplasm with enlarged, note a basophilic cytoplasm with enlarged, hyperchromatic nuclei with enlarged nucleoli. You hyperchromatic nuclei with enlarged nucleoli. You ask the pathologist if she has stained the cells with ask the pathologist if she has stained the cells with high-molecular-weight keratin and, impressed by high-molecular-weight keratin and, impressed by your knowledge, she says she has and points out the your knowledge, she says she has and points out the absence of staining where the basal cell layer is absence of staining where the basal cell layer is normally found.normally found.

The pathologist asks how prostatic cancer is graded. The pathologist asks how prostatic cancer is graded. After you correctly identify the After you correctly identify the Gleason grading systemGleason grading system, she asks about the , she asks about the significance of different Gleason scores.significance of different Gleason scores.

Go toQuestion #5

Gleason ScoreThe Gleason grading system is based on the glandular The Gleason grading system is based on the glandular architecture of prostatic samples under low power:architecture of prostatic samples under low power:▪ ▪ Grade 1 or 2: samples are closely packed, have little Grade 1 or 2: samples are closely packed, have little stroma, and are small and uniform.stroma, and are small and uniform.▪▪ Grade 3: samples have variable-sized glands between Grade 3: samples have variable-sized glands between normal stroma.normal stroma.▪▪ Grade 4: samples have incomplete gland formation.Grade 4: samples have incomplete gland formation.▪▪ Grade 5: samples have no gland formation or lumen Grade 5: samples have no gland formation or lumen appearance, or they may (rarely) be comedocarcinoma.appearance, or they may (rarely) be comedocarcinoma.The Gleason score is the sum of the most commonly found The Gleason score is the sum of the most commonly found pattern and the second most commonly found pattern. The pattern and the second most commonly found pattern. The primary Gleason grade is more important than the second primary Gleason grade is more important than the second one, so Gleason 6 (4+2) is more poorly differentiated than one, so Gleason 6 (4+2) is more poorly differentiated than Gleason 6 (3+3).Gleason 6 (3+3).


Question #5: What Gleason score would suggest that Mr. State’s cancer is poorly differentiated?

A.A. Gleason 2 (1+1)Gleason 2 (1+1)

B.B. Gleason 4 (2+2)Gleason 4 (2+2)

C.C. Gleason 6 (3+3)Gleason 6 (3+3)

D.D. Gleason 10 (5+5)Gleason 10 (5+5)


A.A. Gleason 2 (1+1): Gleason 2 (1+1) is Gleason 2 (1+1): Gleason 2 (1+1) is considered very well-differentiated. considered very well-differentiated.


Normal Gleason 1


B.B. Gleason 4 (2+2): Gleason 4 (2+2) is Gleason 4 (2+2): Gleason 4 (2+2) is considered well-differentiated.considered well-differentiated.


Normal Gleason 2


C.C. Gleason 6 (3+3): Gleason 5-6 is considered Gleason 6 (3+3): Gleason 5-6 is considered moderately differentiated. The primary moderately differentiated. The primary Gleason grade is more important than the Gleason grade is more important than the second one, so Gleason 6 (4+2) is more poorly second one, so Gleason 6 (4+2) is more poorly differentiated than Gleason 6 (3+3).differentiated than Gleason 6 (3+3).

Return toQuestion #5Normal Gleason 3


D.D. Gleason 10 (5+5): Gleason 8-10 is considered Gleason 10 (5+5): Gleason 8-10 is considered poorly differentiated. poorly differentiated.

ContinueCase

Normal Gleason 5

Case ContinuedMr. State’s Gleason score is 7 (4+3).Mr. State’s Gleason score is 7 (4+3).

ContinueCase

Normal

Gleason 4

Gleason 3

Case Continued

Mr. State now inquires about the Mr. State now inquires about the clinical stage clinical stage of his prostate cancer.of his prostate cancer.

Go toQuestion #6

Question #6: Evidence supports the usefulness of which of the following possible staging modalities for localized prostate cancer?

A.A. Pelvic CTPelvic CT

B.B. PSAPSA

C.C. Digital Rectal Exam (DRE) Digital Rectal Exam (DRE)

D.D. Trans-rectal ultrasoundTrans-rectal ultrasound

E.E. Radionuclide bone scanRadionuclide bone scan


A.A. Pelvic CT: Pelvic CT is rarely used to Pelvic CT: Pelvic CT is rarely used to assess whether pelvic lymph nodes are assess whether pelvic lymph nodes are enlarged, a finding that would suggest enlarged, a finding that would suggest possible nodal metastasis. Because lymph possible nodal metastasis. Because lymph node metastasis is exceedingly rare with node metastasis is exceedingly rare with Gleason score Gleason score ≤ 7 and PSA < 10, pelvic ≤ 7 and PSA < 10, pelvic CT is not routinely done with these values CT is not routinely done with these values unless clinically indicated.unless clinically indicated.



B.B. PSA: Serum PSA correlates very roughly PSA: Serum PSA correlates very roughly with tumor extent.with tumor extent.



C.C. DRE: Since prostatic carcinoma is staged DRE: Since prostatic carcinoma is staged by the TNM system, DRE is used to by the TNM system, DRE is used to assess the primary tumor (T stage). assess the primary tumor (T stage). Because lymph node or other metastasis is Because lymph node or other metastasis is exceedingly rare with Gleason score exceedingly rare with Gleason score ≤ 7 ≤ 7 and PSA < 10, no nodal involvement (N0) and PSA < 10, no nodal involvement (N0) or metastasis (M0) is assumed for clinical or metastasis (M0) is assumed for clinical staging purposes.staging purposes.

Go toQuestion #7


D.D. Trans-rectal ultrasound (TRUS): TRUS is Trans-rectal ultrasound (TRUS): TRUS is typically used to direct biopsy, not for typically used to direct biopsy, not for staging.staging.



E.E. Radionuclide bone scan: Bony metastases Radionuclide bone scan: Bony metastases are rare with a PSA < 20 ng/mL. are rare with a PSA < 20 ng/mL. Although radionuclide bone scanning is Although radionuclide bone scanning is very sensitive to detect bony metastasis, it very sensitive to detect bony metastasis, it is not routinely done with a PSA < 10 if is not routinely done with a PSA < 10 if the Gleason score is the Gleason score is ≤ 7.≤ 7.


Question #7: What is the CLINICAL STAGE of Mr. State’s carcinoma?

A.A. TT11NN00MM00

B.B. TT22NN00MM00

C.C. TT33NN11MM00

D.D. TT44NN11MM00

E.E. TT44NN11MM11

Click here to see

the stages

STAGE SUB-STAGE

DEFINITION

T1 Clinically unapparent tumor, not detected by DRE nor visible by imaging

T1a Incidental histologic finding; <5% of tissue resected during TURP

T1b Incidental histologic finding; >5% of tissue resected during TURP

T1c Tumor identified by needle biopsy due to elevated PSA

T2 Confined within the prostate (detectable by DRE, not visible on TRUS)

T2a Tumor involves half of the lobe or less

T2b Tumor involves more than one half of one lobe but not both lobes

T2c Tumor involves both lobes

T3 Tumor extends through the prostate capsule but has not spread to other organs

T3a Unilateral extracapsular extension

T3b Bilateral extracapsular extension

T3c Tumor invades seminal vesicle(s)

T4 Tumor is fixed or invades adjacent structures other than seminal vesicles

T4a Tumor invades bladder neck and/or external sphincter and/or rectum

T4b Tumor invades levator muscles and/or is fixed to pelvic wall Go to

N Stage

Most common

clinical stage

since screening

with PSA was

instituted.

STAGE SUB-STAGE

DEFINITION

Node (N) Regional lymph nodes

N0 No lymph nodes metastasis

N1 Metastasis in single lymph node <2 cm in greatest dimension

N2 Metastasis in single lymph node >2cm but <5 cm in greatest dimension, or multiple lymph nodes, none >5 cm

N3 Metastasis in lymph node >5 cm in greatest dimension

Go toM Stage

STAGE SUB-STAGE

DEFINITION

Metastasis Systemic spread

M0 No distant metastasis

M1a Non-regional lymph node metastasis

M1b Bone metastasis a) Axial skeleton only b) Extending to peripheral skeleton also

M1c Metastasis at other sites



A.A. TT11NN00MM00: T: T11 tumors have a normal digital tumors have a normal digital

rectal exam (DRE). These are the most rectal exam (DRE). These are the most common tumors diagnosed and are common tumors diagnosed and are detected by biopsy following an abnormal detected by biopsy following an abnormal PSA. Since routine PSA screening was PSA. Since routine PSA screening was instituted, this has been by far the most instituted, this has been by far the most common clinical stage of prostate cancer.common clinical stage of prostate cancer.



B.B. TT22NN00MM00: T: T22 tumors are either palpable by DRE or tumors are either palpable by DRE or

visible by trans-rectal ultrasound (TRUS), but are visible by trans-rectal ultrasound (TRUS), but are confined to the prostate. Tconfined to the prostate. T2a2a tumors involve less tumors involve less

than half of one lobe, Tthan half of one lobe, T2b2b involve more than half involve more than half

of one lobe but not both lobes, and Tof one lobe but not both lobes, and T2c2c tumors are tumors are

bilateral. With Mr. State’s PSA of 4.8, no nodal bilateral. With Mr. State’s PSA of 4.8, no nodal metastasis is assumed for the clinical staging, as metastasis is assumed for the clinical staging, as lymph node metastases are exceedingly rare with lymph node metastases are exceedingly rare with Gleason Gleason <<7 and PSA <107 and PSA <10

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C.C. TT33NN11MM00: T: T33 tumors have extracapsular tumors have extracapsular

extension. Textension. T3b3b involves the seminal involves the seminal

vesicles. Nvesicles. N11 indicates nodal involvement. indicates nodal involvement.



D.D. TT44NN11MM00: T: T44 tumors extend into the bladder neck, tumors extend into the bladder neck,

sphincter, levator muscles, pelvic sidewall, or sphincter, levator muscles, pelvic sidewall, or rectum (involvement of the rectum is rare because rectum (involvement of the rectum is rare because of the strength of of the strength of Denonvillier’sDenonvillier’s fascia fascia separating separating the prostate from the rectum). Nthe prostate from the rectum). N11 indicates nodal indicates nodal

involvement. Minvolvement. M11 indicates metastases: M indicates metastases: M1a1a to to

nonregional lymph, Mnonregional lymph, M1b1b to bone (typically to bone (typically

osteoblastic lesions), and Mosteoblastic lesions), and M1c1c to other sites. to other sites.



E.E. TT44NN11MM11: T: T44 tumors extend into the bladder tumors extend into the bladder

neck, sphincter, rectum, levator muscles, neck, sphincter, rectum, levator muscles, or pelvic sidewall. Nor pelvic sidewall. N11 indicates nodal indicates nodal

involvement. involvement.


Case Continued

Mr. State inquires about his different Mr. State inquires about his different treatment options. You explain that the major treatment options. You explain that the major categorical options include watchful waiting, categorical options include watchful waiting, radiation therapy, and radical prostatectomy. radiation therapy, and radical prostatectomy. You recommend the You recommend the National Cancer Institute (NCI) website National Cancer Institute (NCI) website discussion on treatment options.discussion on treatment options.

http://www.nci.nih.gov/cancertopics/understanding-prostate-cancer-treatment/page5

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Case Continued

At this time, he has normal erections At this time, he has normal erections sufficient for penetration and no urinary sufficient for penetration and no urinary incontinence. Despite his high-fat diet, his incontinence. Despite his high-fat diet, his lipid panel is within normal limits and he has lipid panel is within normal limits and he has no other cardiovascular risk factors other than no other cardiovascular risk factors other than smoking and smoking and obesity (BMI 32). obesity (BMI 32). On review of On review of systems, he appears to be in good health.systems, he appears to be in good health.

Continue Case

Case Continued

Mr. State is not enthusiastic about surgery or Mr. State is not enthusiastic about surgery or radiation and says “Doc, if I just wait and radiation and says “Doc, if I just wait and don’t do anything else, won’t I die of don’t do anything else, won’t I die of something else before the prostate cancer something else before the prostate cancer gets me?”gets me?”

Go toQuestion #8

Question #8: What is the likelihood that Mr. State will die of prostate cancer within 10 years if he chooses watchful waiting?

A.A. 1%1%

B.B. 15%15%

C.C. 50%50%

D.D. 95%95%


A.A. 1%: Very few prostate cancers are 1%: Very few prostate cancers are indolent enough to have a 10 year disease-indolent enough to have a 10 year disease-specific mortality of specific mortality of ≤ 1%≤ 1%



B.B. 15%: Results of most watchful waiting studies 15%: Results of most watchful waiting studies suggest a 10-year disease-specific mortality of suggest a 10-year disease-specific mortality of approximately 10-15%, although there is a wide approximately 10-15%, although there is a wide variability based on patient population (4-45%). variability based on patient population (4-45%). Watchful waiting may be an appropriate option Watchful waiting may be an appropriate option for an older patient with many co-morbidities, for an older patient with many co-morbidities, because non-prostate cancer-related mortality is because non-prostate cancer-related mortality is high and the patient is likely to die of another high and the patient is likely to die of another disease before he dies of prostate cancer. disease before he dies of prostate cancer.

Watchful waiting article #1 (Johansson: JAMA 2004)Watchful waiting article #2 (Bil-Axelson: NEJM 2005)

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C. 50%: While some prostate cancers are C. 50%: While some prostate cancers are aggressive enough to result in disease-aggressive enough to result in disease-specific death within 10 years, most are specific death within 10 years, most are less aggressive.less aggressive.



D. 95%: Very few prostate cancers are D. 95%: Very few prostate cancers are aggressive enough to have a 10 year aggressive enough to have a 10 year disease-specific mortality of disease-specific mortality of ≥ 95%≥ 95%


Case Continued After hearing your discussion of the watchful After hearing your discussion of the watchful

waiting option, Mr. State wants to know more waiting option, Mr. State wants to know more about radiation therapy. A family friend who about radiation therapy. A family friend who had prostate cancer 10 years ago and was had prostate cancer 10 years ago and was treated with external beam therapy had treated with external beam therapy had terrible side-effects and discontinued terrible side-effects and discontinued treatment before completing the entire course. treatment before completing the entire course. His cancer recurred within 5 years and he His cancer recurred within 5 years and he passed away. Mr. State is concerned about passed away. Mr. State is concerned about the side-effects of radiation therapy.the side-effects of radiation therapy.

Go to Question #9

Radiation therapy article (Nilsson, Acta Oncol, 2004)

Question #9: Which of the following are potential complications of radiation

treatment?

A.A. FrequencyFrequency

B.B. FatigueFatigue

C.C. ImpotenceImpotence

D.D. Bowel botherBowel bother

E.E. All of the above All of the above


A.A. Frequency: Most patients experience Frequency: Most patients experience urinary frequency and dysuria. Over 90% urinary frequency and dysuria. Over 90% of these cases, however, resolve within of these cases, however, resolve within one year.one year.

Back to Question #9


B. Fatigue: The degree of fatigue is variable, B. Fatigue: The degree of fatigue is variable, but significant in up to 75% of patients but significant in up to 75% of patients during radiation treatment. Within 2-3 during radiation treatment. Within 2-3 months of treatment completion, most months of treatment completion, most patients return to baseline energy levels.patients return to baseline energy levels.

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C. Impotence: Impotence has been reported C. Impotence: Impotence has been reported in up to 35-40% of patients.in up to 35-40% of patients.

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D. Bowel bother: Mild, self-limited rectal D. Bowel bother: Mild, self-limited rectal bleeding is present in approximately 10% bleeding is present in approximately 10% of patients. of patients.

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E. All of the above. Frequency, fatigue, E. All of the above. Frequency, fatigue, impotence, and bowel bother are all impotence, and bowel bother are all potential side-effects of radiation therapy.potential side-effects of radiation therapy.

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Case Continued

Mr. State now inquires about survival rates Mr. State now inquires about survival rates after radiation therapy.after radiation therapy.

Go to Question # 10

Question #10: What are overall and disease-specific 10-year survival after radiation therapy?

A.A. 80% and 90%, respectively80% and 90%, respectively

B.B. 60% and 70%, respectively60% and 70%, respectively

C.C. 40% and 50%, respectively40% and 50%, respectively


A.A. 80% & 90%: Overall 10-year survival after 80% & 90%: Overall 10-year survival after radiation therapy is approximately 80%. radiation therapy is approximately 80%. Disease-specific survival is approximately Disease-specific survival is approximately 90%. These results indicate that 90%. These results indicate that approximately 20% of patients with approximately 20% of patients with prostate cancer treated with radiation prostate cancer treated with radiation therapy die within 10 years, with half therapy die within 10 years, with half (10%) dying of prostate cancer.(10%) dying of prostate cancer. Continue

Case


B. 60% & 70%: Both overall and disease-B. 60% & 70%: Both overall and disease-specific 10-year survival are significantly specific 10-year survival are significantly better than 60% and 70%, respectively.better than 60% and 70%, respectively.



C. 40% & 50%: Both overall and disease-C. 40% & 50%: Both overall and disease-specific 10-year survival are significantly specific 10-year survival are significantly better than 40% and 50%, respectively.better than 40% and 50%, respectively.

..


Case Continued

Mr. State now wants to know more about Mr. State now wants to know more about radical prostatectomy. You explain that the radical prostatectomy. You explain that the procedure entails a 2-3 hour operation that procedure entails a 2-3 hour operation that generally requires a 2-3 day hospital stay. He generally requires a 2-3 day hospital stay. He will be able to donate will be able to donate autologousautologous units of units of blood to minimize the likelihood of blood to minimize the likelihood of transfusion reaction if transfusion becomes transfusion reaction if transfusion becomes necessary. He will have a catheter to drain his necessary. He will have a catheter to drain his bladder for the first 7-10 days after surgery.bladder for the first 7-10 days after surgery.

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Case Continued

You discuss potential complications of radical You discuss potential complications of radical prostatectomy, including blood loss, incontinence, prostatectomy, including blood loss, incontinence, and impotence. You explain that reports of post-and impotence. You explain that reports of post-operative potency after radical prostatectomy vary operative potency after radical prostatectomy vary widely based on surgical techniques, patient widely based on surgical techniques, patient population, and method of data collection. If potency population, and method of data collection. If potency does return, it will typically return within 6-12 does return, it will typically return within 6-12 months post-operatively, with significant variability.months post-operatively, with significant variability.

Go toQuestion #11

Question #11: If he chooses surgery, Mr. State’s post-operative potency will be most strongly influenced by which of the following?

A.A. Tumor sizeTumor size

B.B. Pre-operative PSAPre-operative PSA

C.C. AgeAge

D.D. Surgical techniqueSurgical technique

Baseline potency article (Hu, J Urol 2004)


A.A. Tumor size: Tumor size correlates very Tumor size: Tumor size correlates very roughly with post-operative potency. roughly with post-operative potency. Extremely large tumors, however, are Extremely large tumors, however, are associated with a higher likelihood of associated with a higher likelihood of capsular penetration, often precluding capsular penetration, often precluding nerve-sparing operative techniques.nerve-sparing operative techniques.



B. Pre-operative PSA: Pre-operative PSA B. Pre-operative PSA: Pre-operative PSA correlates very roughly with post-operative correlates very roughly with post-operative potency. PSA>10, however, is associated potency. PSA>10, however, is associated with a higher likelihood of capsular with a higher likelihood of capsular penetration, often precluding nerve-sparing penetration, often precluding nerve-sparing operative techniques.operative techniques.



C. Age: Patient age is the strongest predictive C. Age: Patient age is the strongest predictive factor for post-operative potency. factor for post-operative potency. Increasing age is inversely proportional to Increasing age is inversely proportional to post-operative potency. Reports of potency post-operative potency. Reports of potency rates for men under 60 range from 20-80%, rates for men under 60 range from 20-80%, for men 60-79 from 10-70%, and for men for men 60-79 from 10-70%, and for men >80 years of age from 5-70%. Although >80 years of age from 5-70%. Although surgical technique and other factors also surgical technique and other factors also influence post-operative potency, age is the influence post-operative potency, age is the most important factor.most important factor.

Go to Question #12


D. Surgical technique: Reports of potency D. Surgical technique: Reports of potency rates for men under 60 after bilateral rates for men under 60 after bilateral nerve-sparing operations range from 40-nerve-sparing operations range from 40-80%, but drop to 20-60% after unilateral 80%, but drop to 20-60% after unilateral nerve-sparing operations. The respective nerve-sparing operations. The respective rates are 25-75% and 10-50% in men over rates are 25-75% and 10-50% in men over the age of 60. Surgical technique is not the the age of 60. Surgical technique is not the strongest predictor of post-operative strongest predictor of post-operative potency.potency.


Question #12: If he chooses surgery, what is the likelihood he will be continent of urine within 1 year?

A.A. 10%10%

B.B. 35%35%

C.C. 60%60%

D.D. 85%85%

Continent article (Hu, J Urol 2004)


A. 10%: Most patients are continent of urine A. 10%: Most patients are continent of urine within 1 year.within 1 year.



B. 35%: Most patients are continent of urine B. 35%: Most patients are continent of urine within 1 year.within 1 year.



C. 60%: >60% of patients are continent of C. 60%: >60% of patients are continent of urine within 1 year.urine within 1 year.



D. 85%: The rate of complete post-operative urinary D. 85%: The rate of complete post-operative urinary incontinence is approximately 3%, but the rate of incontinence is approximately 3%, but the rate of mild stress urinary incontinence may be as high mild stress urinary incontinence may be as high as 20%. Return to continence is gradual, with as 20%. Return to continence is gradual, with 50% of patients continent 3 months post-50% of patients continent 3 months post-operatively and approximately 75% continent at operatively and approximately 75% continent at 6 months. Although most patients report no 6 months. Although most patients report no significant incontinence after one year, only 60-significant incontinence after one year, only 60-65% report restoration of 65% report restoration of baselinebaseline continence continence (i.e. they have minor episodes of incontinence (i.e. they have minor episodes of incontinence that they do not deem significant). that they do not deem significant).

ContinueCase

Case Continued

Based on Mr. States clinical exam, PSA and Based on Mr. States clinical exam, PSA and biopsy results you use a biopsy results you use a Partin tablePartin table to to determine there is a 67% likelihood his determine there is a 67% likelihood his prostate cancer is confined to the prostate.prostate cancer is confined to the prostate.

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Case Continued

Mr. State chooses to undergo radical prostatectomy. His final surgical pathology is Gleason (4+3=7) confined to the prostate.

Go to Question #13

Question #13: In this patient, what is the likelihood of disease-free 10 year survival?

A.A. 40%40%

B.B. 60%60%

C.C. 80%80%

D.D. 95%95%

Disease-free 10 year survival article (Roehl, J Urol 2004)


A.A. 40%: Patients with extensive extracapsular 40%: Patients with extensive extracapsular extension have 70% 5-year disease-free extension have 70% 5-year disease-free survival rates and 40% 10-year survival survival rates and 40% 10-year survival rates.rates.



B. 60%: Because he does not have B. 60%: Because he does not have extracapsular extension, the probability of extracapsular extension, the probability of disease-free 10 year survival is better than disease-free 10 year survival is better than 60%.60%.



C. 80%: Patients with organ-confined C. 80%: Patients with organ-confined prostate cancer have approximately 80% prostate cancer have approximately 80% 10-year disease-free survival rates.10-year disease-free survival rates.

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D. 95%: Even if he had extracapsular D. 95%: Even if he had extracapsular extension there would be a >5% possibility extension there would be a >5% possibility of disease-specific 10 year mortality.of disease-specific 10 year mortality.


Case Continued

Mr. State does well after surgery. His catheter Mr. State does well after surgery. His catheter is removed 10 days post-operatively and his is removed 10 days post-operatively and his wounds are well-healed. You schedule a wounds are well-healed. You schedule a follow-up appointment for 3 months.follow-up appointment for 3 months.

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Case Continued

Mr. State comes for a 3 month follow-up. He Mr. State comes for a 3 month follow-up. He has occasional loss of urine when he plays has occasional loss of urine when he plays tennis, but is otherwise fully continent. He has tennis, but is otherwise fully continent. He has begun having satisfactory erections again. begun having satisfactory erections again. You discuss cancer surveillance.You discuss cancer surveillance.

Go toQuestion #14

Question #14: What is the best way to test for recurrence of Mr. State’s prostate cancer?

A.A. Bone scanBone scan

B.B. PSAPSA

C.C. Chest X-rayChest X-ray

D.D. Physical examPhysical exam


A.A. Bone scan: Unnecessary due to the low Bone scan: Unnecessary due to the low likelihood of bone metastasis.likelihood of bone metastasis.



B. PSA: PSA levels should be undetectable B. PSA: PSA levels should be undetectable following radical prostatectomy. This test following radical prostatectomy. This test is typically ordered at the 3 month follow-is typically ordered at the 3 month follow-up visit. Rising PSA levels suggest up visit. Rising PSA levels suggest biochemical disease recurrence.biochemical disease recurrence.

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C. Chest X-ray: Unnecessary due to the low C. Chest X-ray: Unnecessary due to the low likelihood of bone metastasis.likelihood of bone metastasis.



D. Physical exam: Should be performed, but D. Physical exam: Should be performed, but will only identify gross disease, which is will only identify gross disease, which is highly unlikely in this patient.highly unlikely in this patient.


Case Continued

Mr. State’s PSA is undetectable. Mr. State’s PSA is undetectable.

He returns 9 months later (1 year post-operatively) to He returns 9 months later (1 year post-operatively) to recheck his PSA, which is <0.1. He has returned to recheck his PSA, which is <0.1. He has returned to full continence and is having satisfactory erections. full continence and is having satisfactory erections.

He passes away 10 years later of unrelated He passes away 10 years later of unrelated cardiovascular disease.cardiovascular disease.

End case

Thank you.You have successfully completed this

cancer survivorship case.

Start of case

This case was developed by Steve Lerman, MD andJonathan Bergman, MD, Department of Urology

This module was designed by Tatum Langford Korin and Sarah Afrand, Instructional Design & Technology Unit

Cancer Survivorship Grant Project #© 2005, University of California Regents

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Glossary

Dodecad Biopsy: During prostate biopsy, 12 or more Dodecad Biopsy: During prostate biopsy, 12 or more samples are taken to increase the likelihood of samples are taken to increase the likelihood of detecting cancer if it is present.detecting cancer if it is present.

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Glossary

Hypoechoic: A region through which Hypoechoic: A region through which ultrasonography cannot penetrate; this region usually ultrasonography cannot penetrate; this region usually represents a prostatic nodule (red arrows).represents a prostatic nodule (red arrows).

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Prostate transverse

section

Glossary

Autologous: One’s own blood. By donating blood to Autologous: One’s own blood. By donating blood to themselves pre-operatively, patients can decrease the themselves pre-operatively, patients can decrease the risk of transfusion reaction if they require an risk of transfusion reaction if they require an intraoperative or postoperative blood transfusion. intraoperative or postoperative blood transfusion. Donation is done a few months prior to the procedure Donation is done a few months prior to the procedure so the patient’s red blood cell count can re-stabilize.so the patient’s red blood cell count can re-stabilize.

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Partin Tables

Partin coefficient tables estimate prognosis by Partin coefficient tables estimate prognosis by determining four probabilities:determining four probabilities:

1)1) The probability that the patient has completely organ-The probability that the patient has completely organ-confined diseaseconfined disease

2)2) The probability that the patient has “established The probability that the patient has “established capsular penetration”capsular penetration”

3)3) The probability that the patient has extension of his The probability that the patient has extension of his prostate cancer into his seminal vesiclesprostate cancer into his seminal vesicles

4)4) The probability that the patient has prostate cancer The probability that the patient has prostate cancer which has spread into his lymph nodeswhich has spread into his lymph nodes

Return to casePartin Table (word document)

Gleason ScoreThe Gleason grading system is based on the The Gleason grading system is based on the glandular architecture of prostatic cells under low glandular architecture of prostatic cells under low power. Grade 1 or 2 cells are closely packed, have power. Grade 1 or 2 cells are closely packed, have little stroma, and are small and uniform. Grade 3 little stroma, and are small and uniform. Grade 3 cells have variable-sized glands between normal cells have variable-sized glands between normal stroma. Grade 4 cells have incomplete gland stroma. Grade 4 cells have incomplete gland formation. Grade 5 cells have no gland formation or formation. Grade 5 cells have no gland formation or lumen appearance, or they may (rarely) be lumen appearance, or they may (rarely) be comedocarcinoma. The Gleason score is the sum of comedocarcinoma. The Gleason score is the sum of the most commonly found cell and the second most the most commonly found cell and the second most commonly found cell. The primary Gleason grade commonly found cell. The primary Gleason grade is more important than the second one, so Gleason 6 is more important than the second one, so Gleason 6 (4+2) is more poorly differentiated than Gleason 6 (4+2) is more poorly differentiated than Gleason 6 (3+3).(3+3).

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Clinical versus Pathological Staging

Clinical staging of prostate cancer involves Clinical staging of prostate cancer involves estimation of disease extent based on estimation of disease extent based on physical examination, laboratory studies, and physical examination, laboratory studies, and imaging studies. Pathological staging imaging studies. Pathological staging involves analysis of the removed specimen, involves analysis of the removed specimen, as well. The pathologic stage of prostate as well. The pathologic stage of prostate cancer is as advanced as the clinical stage in cancer is as advanced as the clinical stage in 30% of cases, more advanced in 70% of 30% of cases, more advanced in 70% of cases, and rarely less advanced.cases, and rarely less advanced.

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Clinical versus Pathological Staging

Clinical staging of prostate cancer involves Clinical staging of prostate cancer involves estimation of disease extent based on estimation of disease extent based on physical examination, laboratory studies, and physical examination, laboratory studies, and imaging studies. Pathological staging imaging studies. Pathological staging involves analysis of the removed specimen, involves analysis of the removed specimen, as well. The pathologic stage of prostate as well. The pathologic stage of prostate cancer is as advanced as the clinical stage in cancer is as advanced as the clinical stage in 30% of cases, more advanced in 70% of 30% of cases, more advanced in 70% of cases, and rarely less advanced.cases, and rarely less advanced.


Denonvillier’s fascia

Denonvillier’s fascia

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Disease-Free Survival

Disease-free survival is the length of time a Disease-free survival is the length of time a patient lives with no evidence of the disease patient lives with no evidence of the disease in question. If a prostate cancer patient were in question. If a prostate cancer patient were alive 10 years after radical prostatectomy, but alive 10 years after radical prostatectomy, but with a rising PSA, the patient would be with a rising PSA, the patient would be categorized as a cancer survivor, but not a categorized as a cancer survivor, but not a disease-free survivor.disease-free survivor.


Obesity

Obesity is currently defined by body mass Obesity is currently defined by body mass index (BMI). A BMI of 25-29 kg/mindex (BMI). A BMI of 25-29 kg/m22 is is overweight, 30-39 kg/moverweight, 30-39 kg/m22 is obese, and >40 is obese, and >40 kg/mkg/m22 is morbidly obese. is morbidly obese.

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Disease-Free Survival

Disease-free survival is the length of time a Disease-free survival is the length of time a patient lives with no evidence of the disease patient lives with no evidence of the disease in question. If a prostate cancer patient were in question. If a prostate cancer patient were alive 10 years after radical prostatectomy, but alive 10 years after radical prostatectomy, but with a rising PSA, the patient would be with a rising PSA, the patient would be categorized as a cancer survivor, but not a categorized as a cancer survivor, but not a disease-free survivor.disease-free survivor.


Documents

Cancer Survivorship Prostate Cancer Risks and Treatments © 2005 University of California Regents Cancer Survivorship Grant Start Case Photo collection