1. Prostate Needle Biopsy: The Pitfalls and the Role of the Pathologist – Patient Track Prostate Cancer Symposium “Intriguing Cases / Emerging Strategies in Awareness and Management” The Prostate Net October 6, 2009 New York, NY Angelo M. De Marzo, MD PhD The Johns Hopkins University School of Medicine, Departments of Pathology, Urology and Oncology, The Brady Urological Research Institute, The Kimmel Comprehensive Cancer Center at Johns Hopkins

2. What is a Pathologist? All biopsy tissue is sent to a pathologist who uses a microscope to determine the diagnosis (e.g. cancer or not)

3. What is a prostate biopsy? Usually 8-12 or more “cores” of tissue are taken using Transrectal Ultrasound (TRUS) guidance. Actual Prostate Core Needle Biopsies Under Microscope: Low Magnification

4. What if cancer is not present on biopsy? If the biopsy diagnosis is: Atypical: “Small focus of atypical gland suspicious for but not diagnostic of cancer” “Atypical small acinar proliferation” (ASAP) Up to 50% (or more) of men with a diagnosis of atypical will be found to have cancer on a repeat biopsy Most recommend a repeat biopsy High grade PIN a repeat biopsy should be based on a number of factors that you discuss with your physician

5. What if cancer is not present on biopsy? If biopsy is called benign: For example benign prostatic tissue; should not be called BPH Inflammation (acute or chronic) Since the biopsy sampling technique is imperfect, up to 20% (or more) of men with a negative prostate biopsy may be found to have cancer on a repeat biopsy The decision for a repeat biopsy should be based on a number of factors that you discuss with your physician

6. What you need to know from your prostate biopsy results if there is cancer present Gleason Grading What is the Gleason score? (two separate numbers from 1-5 added together; most common is 3+3=6) What is the number of tissue cores positive for cancer and what is the total number of tissue cores taken? Gleason Score Grade 2-6: low aggressiveness Grade 8-10: high aggressiveness Grade 7: intermediate aggressiveness

7. Gleason Patterns Gleason Pattern 3 Gleason Pattern 5 Microscopic appearance of prostate cancer (adenocarcinoma) under higher magnification

8. Active Surveillance Some patients with limited Gleason score 6 (e.g. less than 3 cores positive and no core with more than 50% cancer) elect to forego immediate treatment and undergo active surveillance A potential pitfall with this is: Up to 25% of patients with a Gleason grade 6 tumor on biopsy will be found to have a Gleason 7 or higher if their prostate is removed Researchers are attempting to find biological factors in the biopsy to help predict who will have higher grade or more aggressive disease The “good news” is that even in men who “progress” to more advanced pathology on an active surveillance program, most still have curable disease when the prostate is removed Most “progression” events occur within 2 years suggesting that undersampling, rather than disease progression, is responsible J. Urology, Vol. 181, 1628-1634, April 2009 J. Urology, Vol. 182, 2274-2279, November 2009

9. Discussion Topics Should I get a second opinion on my pathology slides? Should I get my prostate biopsy tissue evaluated by Aureon Laboratories Prostate Px+?