Cancer Survivorship

Cancer Survivorship Prostate Cancer Risks and Treatments Photo collection is courtesy of PEIR - University of Alabama at Birmingham Department of Pathology via the HEAL (Health Education Asset Library) database Start Case © 2005 University of California Regents Cancer Survivorship Grant

Goal of this Module This is an interactive and self-directed learning module intended to build a foundation of knowledge around the epidemiology and late effects of cancer survival. This is one of several educational modules you will complete during your core clinical clerkships. Themes emphasized in this, and other modules, are: • Epidemiology of survival • Late effects • Psychosocial concerns • Secondary prevention • Strategies for behavior change Meet your patient

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

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

Question #1: Which of Mr. State’s risk factors poses the largest relative risk for prostate cancer? • Ethnicity • Age • Family History • Diet • Environmental Exposure

Question #1: Incorrect Answer • Ethnicity: African-Americans are at higher risk for prostate cancer than matched Caucasians. On average, they present with more advanced disease at initial diagnosis. The potential increased mortality for African-Americans compared to Caucasians is controversial. Prostate cancer screening should begin at 40 years of age for African-Americans. Ethnicity does not pose the largest relative risk in this patient. Return to Question #1 Ethnicity article (Kang, BJU 2004)

Question #1: Correct Answer • Age: The incidence of prostate cancer increases with age. Clinically significant prostate cancer develops in 0.01% of men<40 years old, 1% of men 40-59 years old, and 13% of men over the age of 60. Age article (Thompson, NEJM 2004) Continue case

Question #1: Incorrect Answer C. Family History: The age at which the disease was diagnosed in a first-degree family member is vital to determining the relative risk for Mr. State. The relative risk for prostate cancer is 4-7x 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 age of onset was 70 years old. Prostate cancer screening should begin at 40 years of age for patients with a family history of prostate cancer. Return to Question #1 Family history article (Thompson, NEJM 2004)

Question #1: Incorrect Answer D. Diet: Although high fat intake doubles Mr. States risk of prostate cancer, diet does not pose the largest relative risk. Return to Question #1 Diet article (Mazhar: BJU 2004)

Question #1: Incorrect Answer E. Environmental exposure: His risk of prostate cancer increases with exposure to alkaline batteries, welding chemicals, and, possibly, tobacco (all contain cadmium, which is carcinogenic in the prostate.) However, these exposures do not pose the largest relative risk. Environmental exposure article (Deutsch: Lancet Oncol 2004) Return to Question #1

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

Case Continued On rectal exam, sphincter tone is normal. The prostate margins are distinct and it appears to be normal in size, but a firm, 0.5 cm x 0.5 cm nodule is palpated along the right lateral sulcus. After the exam, you remember to check Mr. State’s labs on the computer. CBC and 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? • PSA velocity • Age-adjusted PSA • PSA density • Ratio of free PSA to bound PSA • None of the above

Question #2: Incorrect Answer A. PSA velocity: A change in PSA (PSA velocity) of >1.5 ng/mL over 2 years may be associated with prostate cancer. However, the same laboratory should be used, and even then PSA velocity has a low sensitivity and specificity for prostate cancer. PSA velocity article (D’ Amico: NEJM 2004) Return to Question #2

Question #2: Incorrect Answer B. Age-adjusted PSA: Adjusting PSA for age increases the sensitivity for younger men and specificity for older men. The 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 for 60-69 year olds, and 0-6.5 for 70-79 year olds. However, PSA is useful only as a screening tool, not for definitive diagnosis. Return to Question #2 Age-adjusted PSA article (Chu, Cancer 2002)

Question #2: Incorrect Answer C. PSA density: The PSA density adjusts for benign prostatic hyperplasia (BPH), since 1 gram of BPH tissue elevates PSA by approximately 0.12 ng/mL. While a PSA density >0.15 is more likely to warrant a biopsy, it only raises the positive predictive value to 30-40%. Return to Question #2 PSA density (D’Amico: NEJM 2004)

Question #2: Incorrect Answer D. Ratio of free PSA to bound PSA: Normally, approximately 90% of PSA is bound to alpha-1-antichymotrypsin. Free PSA levels below 21% tend to correlate with prostate cancer, while levels above 21% are often seen in older men whose disease is slowly progressing. These ratios, however, must be correlated with other studies. Return to Question #2 Ratio of free PSA to bound PSA article (Uemura: Int J Urol 2004)

Question #2: Correct Answer E. None of the above: PSA>4ng/mL has a positive predictive value of 20-30% for carcinoma of the prostate. While each of the above adjustments is useful in improving the sensitivity and specificity of the test to some extent, PSA should still be used to guide a further work-up and should be considered in the context of the patient’s other personal risk factors, history, physical exam, and other findings. PSA may be elevated secondary to BPH, urethral instrumentation, infection, prostatic infarction, or prostatic massage. The only way to definitively diagnose prostate cancer is with biopsy. Continue case

Case Continued You tell Mr. State that you would like to perform a trans-rectal ultrasound (TRUS)-guided biopsy. He argues that it is an uncomfortable procedure and says he doesn’t see the point, but Mrs. State chides him that “the doctor knows best”. He agrees to the procedure. Before performing the TRUS, you try to predict where a potential cancer might be found. Go to Question #3

TRUS-Guided Bx 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. Back to case

Question #3: In which zone of the prostate will carcinoma most likely arise? • Transition zone • Peripheral zone • Central zone • Anterior fibromuscular area

Question #3: Incorrect Answer • Transition zone: 10-20% of prostatic carcinoma arises in the transition zone. Benign prostatic hyperplasia almost always occurs in the transition zone. Return to Question #3

Question #3: Correct Answer B. Peripheral zone: 65-70% of prostatic carcinoma arises in the peripheral zone. The peripheral zone can be palpated on digital rectal exam (DRE), making DRE a useful screening tool for prostate cancer. Continue case

Question #3: Incorrect Answer C. Central zone: About 5% of prostate cancer arises in the central zone. Return to Question #3

Question #3: Incorrect Answer D. Anterior fibromuscular area: Prostatic cancer rarely arises in the anterior fibromuscular area. Return to Question #3

Case Continued After pre-medication with broad-spectrum antibiotics, TRUS is performed and shows a hypoechoic pattern in the peripheral zone and the left base. Core biopsies of the hypoechoic area are taken and random sampling is done by dodecad biopsies. You go to the pathology lab to review the findings so you can sound smart if your attending questions you. To your dismay, the pathologist asks you a series of 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? • Small cell carcinoma • Sarcoma • Adenocarcinoma • Transitional cell carcinoma

Question #4: Incorrect Answer • Small cell carcinoma: Small cell carcinomas account for less than 1% of prostate cancer. Return to Question #4

Question #4: Incorrect Answer B. Sarcoma: Sarcomas account for less than 1% of prostate cancer. Return to Question #4

Question #4: Correct Answer C. Adenocarcinoma: Adenocarcinomas account for over 95% of prostate cancers. The distinguishing histologic characteristic of prostate cancer is the absence of basal cells, which can be seen with high-molecular-weight keratin staining (which stains basal cells). Absence of staining is consistent with carcinoma of the prostate. Continue case

Question #4: Incorrect Answer D. Transitional cell carcinoma: Transitional cell carcinomas account for approximately 4% of prostate cancer. They do account for over 90% of bladder cancer. Return to Question #4

Case Continued Upon viewing the slides with the pathologist, you note a basophilic cytoplasm with enlarged, hyperchromatic nuclei with enlarged nucleoli. You ask the pathologist if she has stained the cells with high-molecular-weight keratin and, impressed by your knowledge, she says she has and points out the absence of staining where the basal cell layer is normally found. The pathologist asks how prostatic cancer is graded. After you correctly identify the Gleason grading system, she asks about the significance of different Gleason scores. Go to Question #5

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

Question #5: What Gleason score would suggest that Mr. State’s cancer is poorly differentiated? • Gleason 2 (1+1) • Gleason 4 (2+2) • Gleason 6 (3+3) • Gleason 10 (5+5)

Question #5: Incorrect Answer • Gleason 2 (1+1): Gleason 2 (1+1) is considered very well-differentiated. Normal Gleason 1 Return to Question #5

Question #5: Incorrect Answer B. Gleason 4 (2+2): Gleason 4 (2+2) is considered well-differentiated. Normal Gleason 2 Return to Question #5

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

Question #5: Correct Answer D. Gleason 10 (5+5): Gleason 8-10 is considered poorly differentiated. Normal Gleason 5 Continue Case

Case Continued Mr. State’s Gleason score is 7 (4+3). Gleason 4 Normal Continue Case Gleason 3

Case Continued Mr. State now inquires about the clinical stage of his prostate cancer. Go to Question #6

Question #6: Evidence supports the usefulness of which of the following possible staging modalities for localized prostate cancer? • Pelvic CT • PSA • Digital Rectal Exam (DRE) • Trans-rectal ultrasound • Radionuclide bone scan

Question #6: Incorrect Answer • Pelvic CT: Pelvic CT is rarely used to assess whether pelvic lymph nodes are enlarged, a finding that would suggest possible nodal metastasis. Because lymph node metastasis is exceedingly rare with Gleason score ≤ 7 and PSA < 10, pelvic CT is not routinely done with these values unless clinically indicated. Return to Question #6

Question #6: Incorrect Answer B. PSA: Serum PSA correlates very roughly with tumor extent. Return to Question #6

Question #6: Correct Answer C. DRE: Since prostatic carcinoma is staged by the TNM system, DRE is used to assess the primary tumor (T stage). Because lymph node or other metastasis is exceedingly rare with Gleason score ≤ 7 and PSA < 10, no nodal involvement (N0) or metastasis (M0) is assumed for clinical staging purposes. Go to Question #7

Question #6: Incorrect Answer D. Trans-rectal ultrasound (TRUS): TRUS is typically used to direct biopsy, not for staging. Return to Question #6

Question #6: Incorrect Answer E. Radionuclide bone scan: Bony metastases are rare with a PSA < 20 ng/mL. Although radionuclide bone scanning is very sensitive to detect bony metastasis, it is not routinely done with a PSA < 10 if the Gleason score is ≤ 7. Return to Question #6

Question #7: What is the CLINICALSTAGEof Mr. State’s carcinoma? • T1N0M0 • T2N0M0 • T3N1M0 • T4N1M0 • T4N1M1 Click here to see the stages

Most common clinical stage since screening with PSA was instituted. Go to N Stage

Go to M Stage

Return to Question #7

Cancer Survivorship