1. Prostate Cancer: Causes, Diagnosis, and Treatment Options Bruce B. Garber, MD, FACS Clinical Associate Professor Drexel University College of Medicine Graduate Hospital Philadelphia, PA

2. Introduction Introduction The prostate: The prostate: -is a gland located below the bladder -is a gland located below the bladder -is only present in men -is only present in men -surrounds the urethra -surrounds the urethra -can undergo benign or malignant change -can undergo benign or malignant change

3. -Urine flows from the bladder through the urethra, which is surrounded by the prostate -An enlarged prostate can cause difficulty passing urine -The prostate is not in the rectum, but can be palpated during a digital rectal exam

4. Incidence -Lung, colon, breast, and prostate cancer are the most common solid organ cancers common solid organ cancers -Over 200,000 men are diagnosed with prostate cancer each year in the U.S. cancer each year in the U.S. -African-American men have the highest incidence

5. Prostate Cancer: US Mortality and Incidence, 1973– 1997 SEER Cancer Statistics Review 1973-1997. National Cancer Institute. Bethesda, MD.

6. Prostate Cancer: Causes Prostate Cancer: Causes Risk Factors Currently Under Investigation: ä Racial origin: African American > all other races ä Dietary factors: fatty foods implicated ä Genetic factors: familial prostate cancer; prostate cancer genes have been discovered

7. Prostate Cancer: Diagnosis Prostate Cancer: Diagnosis Methods of Detection: 1. Prostate exam (digital rectal exam, DRE) 2. Prostate-specific antigen (PSA) blood test (free, total, complexed, velocity) (free, total, complexed, velocity) ä If either is abnormal: –Ultrasound-guided prostate needle biopsy

8. Gleason Pathologic Scoring System for Prostate Cancer Gleason DF. In: Tannenbaum M, ed. Urologic Pathology: The Prostate. Philadelphia, Pa: Lea & Febiger; 1977:171-197.

9. Prostate Cancer Staging Systems Prostate Cancer Staging Systems ä Stages A, B, C, D ä TNM system (stage T1C is most common)

10. Whitmore-Jewett Classification Stage A Microscopic cancer confined to the prostate and too small to be felt by digital rectal exam A1 Cancer well differentiated and confined to one site A2 Cancer moderately or poorly differentiated or present in more than one site

11. Whitmore-Jewett Classification Stage B Cancer large enough to be felt on DRE B1 Small nodule on one lobe of prostate B2 Large nodule, several small nodules, or a nodule containing poorly differentiated cells

12. Whitmore-Jewett Classification Stage C A large cancer involving nearly the entire gland C1 Cancer may have spread a small distance beyond the gland C2 Cancer has invaded the neighboring tissue

13. Whitmore-Jewett Classification Stage D Widespread (metastatic) cancer D1 Cancer in pelvic lymph nodes D2 Cancer in bone or other organs

14. Prostate Cancer: Treatment Options Prostate Cancer: Treatment Options Non-curative therapies: 1. Androgen deprivation 1. Androgen deprivation-LHRH-agonists -Bilateral orchiectomy -Antiandrogens 2. Chemotherapy 2. Chemotherapy 3. Observation 3. Observation Potentially curative therapies: 1. Radical prostatectomy RetropubicRetropubic PerinealPerineal Laparoscopic/RoboticLaparoscopic/Robotic 2. Radiotherapy External beam radiationExternal beam radiation Brachytherapy (radioactive seed implant)Brachytherapy (radioactive seed implant) 3. Cryo (freezing)

15. Lupron Depot ® is a registered trademark of TAP Pharmaceuticals, Inc. Copyright © 2001 Bayer Corporation. Viadur™ is a trademark of ALZA Corporation under license to Bayer Corporation. Eulexin ® is a registered trademark of Schering-Plough Pharmaceuticals. Nilandron  is a registered trademark of Aventis. Non-curative Hormonal Therapy: Currently Available Agents LHRH-agonists: ä Zoladex ® (goserelin acetate implant) ä Lupron Depot ® (leuprolide acetate for depot suspension) ä Viadur™ (leuprolide acetate implant) ä Eligard ® ä ® ä Vantas ® Antiandrogens: ä Casodex ® (bicalutamide) ä Eulexin ® (flutamide) ä Nilandron  (nilutamide)

16. Therapies of Curative Intent: Therapies of Curative Intent: ä Radical prostatectomy (total prostate removal) –Retropubic (abdominal incision) –Perineal (incision under scrotum) –Laparoscopic/Robotic (multiple ports) ä Radiotherapy –External beam radiation –Brachytherapy (radioactive seed implant) ä Cryoablation (freezing)

17. Radical Prostatectomy Radical Prostatectomy Advantages ä Can remove all the cancer Disadvantages ä Major operation ä Erectile dysfunction ä Incontinence ä Scar tissue ä Rectal injury ä Wound infection, blood clots, heart attack, etc. ä Often doesn’t remove all of the cancer

18. External Beam Radiation (EBRT) External Beam Radiation (EBRT) Advantages ä Efficacy similar to prostatectomy ä Outpatient Disadvantages  Erectile dysfunction  Chronic bowel and bladder irritation (cystitis, proctitis)  Requires roughly 7 weeks of daily treatment daily treatment  Increased risk of rectal & bladder cancer!

19. Brachytherapy (radioactive seed implant) Brachytherapy (radioactive seed implant) Advantages ä Efficacy similar to EBRT or surgery ä Outpatient; one treatment Disadvantages ä Chronic bowel & bladder irritation irritation ä Erectile dysfunction ä Seed migration 33% ä Can’t treat large prostates ä Increased risk of rectal & bladder cancer!

20. Cryoablation of the Prostate (Cryosurgery, Cryotherapy) CRYO = GREEK WORD FOR COLD ABLATION = DESTRUCTION Cryoablation of the Prostate (Cryosurgery, Cryotherapy) CRYO = GREEK WORD FOR COLD ABLATION = DESTRUCTION

21. What is Cryoablation? What is Cryoablation? ä Cryoablation: cancer treatment by freezing to -40º Centigrade ä No surgical incision, minimal blood loss, no radiation ä Immediate cancer cell death ä Dead cells are slowly reabsorbed by the body ä Outpatient procedure, with rapid return to normal activities ä FDA-approved, covered by Medicare & most carriers ä New technology: <2% of Urologists currently offering Cryoablation

22. ä Transrectal ultrasound guided ä Transperineal placement of 6-8 cryo (freezing) probes ä Transperineal placement of 5-6 temperature sensing probes ä Urethral warming device to preserve urethra & limit side effects TARGETED CRYOABLATION OF THE PROSTATE (TCAP)

23. Technology Temperature shown in real time Argon gas freezes prostate rapidly with excellent control Two freeze/thaw cycles immediately kill cancer cells Total procedure time about 60-90 minutes Computer creates “map” of the prostate Provides real-time guidance Identifies and guides probe placement

24. Current Technology: 6-8 Probe Argon Cryosurgery System, Total Gland Ablation ä 6-8 Cryo probes in prostate ä 5-6 Temperature monitoring probes probes ä Argon Gas = rapid response, excellent freeze control ä Helium Gas = rapid thawing

25. Prostate Cryoablation Probes inserted in between scrotum & rectum Transrectal ultrasound guides the procedure

26. Targeted Cryoablation of the Prostate (TCAP) Before Before Probes Placed Probes Placed Prostate frozen Prostate frozen

27. Prostate Cryoablation Techniques ä Total Gland Ablation ä Nerve-Sparing ä Focal

28. Total Prostate Cryoablation Total Prostate Cryoablation

29. Nerve-Sparing Prostate Cryoablation Nerve-Sparing Prostate Cryoablation

30. Focal Prostate Cryoablation Focal Prostate Cryoablation

31. Results of Total Prostate Cryoablation ä 89% of 590 men followed for 7 years were disease-free based on PSA levels, 87% were disease-free on repeat biopsy ä Rate of rectal injury: 0 - 0.5% ä Rate of urinary incontinence: <5% ä Erectile dysfunction common, but can be successfully treated in almost all men

32. Cryoablation Advantages ä Outpatient ä Minimally-invasive ä Can treat radiation failures ä Can be repeated ä Better than radiation for high grade cancer (Gleason 7-10) Disadvantages ä Erectile dysfunction ä Urinary problems (short-term) ä Shorter track record than surgery or radiation

33. Summary: Prostate Cryoablation ä A well-established treatment for localized prostate cancer ä Covered by Medicare & most carriers ä Minimally invasive: no surgical incision ä Minimal blood loss--blood transfusion not needed ä Better than radiation for high risk (e.g. high Gleason score) disease ä Can treat cancer recurrence after radiation (EBRT or seeds) ä Does not increase risk of rectal or bladder cancer ä Avoids radiation cystitis and proctitis ä Avoids seed migration seen with brachytherapy ä Can be combined with hormonal therapy ä Outpatient procedure for most men ä Unlike any other treatment, can be repeated if necessary ä Rapid return to normal activities ä More rapid recovery than after radical prostatectomy ä Erectile dysfunction frequent but treatable