Keynote Address Overview of Prostate Cancer Treatment Options

1. Keynote AddressOverview of Prostate Cancer Treatment Options William Catalona, MD Professor Northwestern University Feinberg School of Medicine
Department of Urology

2. Overview of Prostate Cancer Treatment Options William J Catalona MD Director, Clinical Prostate Cancer Program Robert H Lurie Comprehensive Cancer Center Northwestern

3. Purpose • Provide brief overview of treatments, discussing advantages and disadvantages • In reporting differences, attempt to be objective • Acknowledge my personal editorial perspective • For balance, refer to contrary opinions

4. Disclose Partners from Industry • Beckman Coulter, Inc – manufacturer of PSA tests • OHMX, Inc - developer of urine PSA test • deCODE genetics, Inc - developer of genetic tests for prostate cancer

5. U.S. Prostate Cancer Statistics 2010 • 217,730 new cases • Most common malignancy • Accounts for 28% of all male cancer • 32,050 deaths from prostate cancer • 11% of all male cancer deaths • Second only to lung cancer Ca: Cancer Journal for Clinicians 2010;60:277-300

6. 2010 Prostate Cancer Statistics DD

7. Incidence DD

8. Deaths PSA ERA DD

9. Relative 5-Year Survival DD

10. Early Detection PSA Screening Saves Lives

11. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) • Screened men had 40% fewer advanced PC at diagnosis • 20% lower prostate cancer death rate in screening arm • (27% lower in men actually screened) • Mortality benefit observed largely in men aged 55-69 Schroder FH et al, NEJM 360:1320, 2009

12. Prostate Cancer-Specific Mortality with Minimal or No Co-Morbidity in PLCO Trial 44% ↓ in PCa-Specific Mortality Controls Screened Crawford ED et al. J Clin Oncol 29:355, 2010

13. GöteborgResults • 41% decrease in advanced disease in screening arm • 66% lower in men actually screened • 44% decrease in PCa mortality in screening arm • 56% lower in men actually screened Hugosson, J, et al. Lancet Oncol 2010; 11: 725–732

14. Active Surveillance

15. Rationale for Active Surveillance Low-risk tumors generallygrow slowly, so there may be time to “watch” them while retaining option for treatment if they show signs of progression on repeat PSA testing or repeat biopsy

16. Caveats • There may be biopsy sampling errors, i.e., the tumor may be worse than the biopsy shows • Some low-grade tumors may become more aggressive over time • In watchful-waiting studies, prostate cancer death rates are generally low for men with a low-grade tumors in the short term, but a marked increase in prostate cancer progression and death with long-term follow-up has been reported

17. With time, all active surveillance studies have shown • Significant under-grading or under-staging of some tumors • Some patients develop metastases • Some die of prostate cancer

18. The criteria for low-risk prostate cancer are wrong 1/3 of the time • Biopsy is correct 95% of the time when it shows “high-risk” tumor features • But is correct only 66% of the time when the biopsy suggests low-risk features Epstein et al J Urol 160: 2407, 1998;Epstein et al, JAMA 271:368, 1994

19. Diffusion Weighted Imaging with MRI T2W MRI and ADC map • Tumors more likely to be visible on DWI if higher grade • True sometimes, but not highly accurate Woodfield et al. AJR 194:316-22, 2011 Lower Apparent diffusion coefficient (ADC) correlated with grade and % tumor involvement on biopsy

20. An example of misleading MRI imaging studies • In 96 potential candidates for active surveillance who had MRI imaging but chose to have surgery instead • 24% had a high Gleason grade or cancer that had spread beyond the prostate • MRI did not significantly which patients had these adverse tumor features NCCN Guidelines: “The timing and value of periodic imaging studies in AS has not been determined.” Ploussard G, et al. BJU Int 2010. Epub

21. Active surveillance has risks • Risks of repeat prostate biopsies • Discomfort of having repeated prostate biopsies • Infections, bleeding, urinary difficulties • Possible erectile dysfunction with multiple biopsies • Anxiety of living with untreated prostate cancer • Non-compliance with regular follow-up protocol • Possible increased complexity of delayed treatment with more side effects (postoperative radiation or hormone therapy) • Progression to metastases or prostate cancer death while on surveillance 1Finelli A, et al. Eur Urol 2011;59:509-14

22. Treatment is compromised for some • For some patients, active surveillance amounts to delayed treatment of cancer • Repeated biopsies are: • Still subject to sampling errors • may induce inflammation that cause increased PSA levels • may cause scarring that makes nerve-sparing surgery difficult or impossible and may compromise surgical margins

23. An example of low cure rate with delayed treatment • The University of Toronto • 50% of patients who received delayed treatment had PSA failure • They are beginning to see some prostate cancer deaths Klotz L et al ,J Clin Oncol 28:126,2009 Johansson JE et al JAMA 291:2713,2004

24. Early treatment has advantages • Patients are more likely to be cured with fewer side effects from treatment • Patients are less likely to require multiple types of treatment to control the cancer

25. An example of early RP decreasing progression to metastases and reducing cancer-specific and all-cause mortality

26. Radical Prostatectomy versus Watchful Waiting for Early Prostate Cancer

27. Conclusion Active surveillance is a reasonable option in men with a limited life expectancy, but should be considered investigationalin men with >10 year life expectancy (younger than 73 years old)

28. Surgical Approaches to Radical Prostatectomy OPEN VS DA VINCI ROBOTIC

29. Long-Term Results • The long-term results of open radical prostatectomy are well documented • Long-term robotic prostatectomy results are not yet available

30. Continence (No Pads)

31. Potency (with or without Viagra-like drugs)

32. Recurrence-Free Survival (PSA <0.1) PSA recurrence- Overall Population

33. Prostate Cancer-Specific Survival Prostate-cancer specific survival

34. Robotic Laparoscopic Prostatectomy • Console

35. Marketing the Robot • Quicker recovery • Less pain • Shorter hospital stay • Quicker return to normal activity • Shorter catheterization • Better visualization • Less bleeding • Better potency • Better continence • Fewer positive margins • Better cosmesis

36. It is claimed that 70% of radical prostateactomies are performed robotically In 2008, in Florida 4,542 radical prostatectomies were performed 1,188 (26%) were robotic and 3,354 (74%) were open

37. Eur Urol. 2010 Jun;57(6):930-7. Epub 2010 Jan 26. Low quality of evidence for robot-assisted laparoscopic prostatectomy: results of a systematic review of the published literature. Kang DC, Hardee MJ, Fesperman SF, Stoffs TL, Dahm P. Department of Urology, University of Florida, Gainesville, FL 32610-0247, USA. 12 surgeons co-authored 72% of the published studies on robotic prostatectomy. “The published RALP literature is limited to observational studies of mostly low methodologic quality.” “Our findings draw into question to what extent valid conclusions about the relative superiority or equivalence of robotic prostatectomy to other surgical approaches can be drawn and whether published outcomes can be generalized to the broader community. “

38. 4.45-fold more RALP patients regretted their decision to have that type of surgery “Patients who underwent RALP were more likely to be regretful and dissatisfied, possibly because of higher expectation of an ‘innovative’ procedure.”

39. Care Path Essentially equivalent

40. “The results of this prospective study have shown that both robotic and conventional radical prostatectomy provide comparable short-term postdischarge recovery, including time to normal and full activity, driving, and post-discharge narcotic use.”

41. Bleeding With good open surgical technique, there is no significant difference in blood transfusion rate

42. Positive Surgical Margin Rates with Open and Robotic Nerve-Sparing Prostatectomy Williams SB et al, Urology 2010 950 cases performed by 2 high-volume surgeons at Brigham and Women’s Hospital (Harvard) Analysis of results was adjusted for known preoperative predictors of positive surgical margins

43. Invasiveness and Cosmesis

44. Robotic: five 1 inch-incisions + one 2 inch incision • Open: one 4-5 inch incision

45. Human Touch and Access • Robotic surgery - cannot feel tissues or appreciate how easily tissues separate from one another • More complete access with open surgery

46. “Visual and tactile assessment during open surgery by an experienced surgeon provides valuable information on when and where it is safe to preserve the neurovascular bundles…”

47. Potency Continence

48. Burning the Prostate Out Compromises Nerve Sparing • The greater use of electricity or heat with robotic surgery to control bleeding can cause irreversible damage to the neurovascular bundles

49. Comparative Effectiveness of Robotic vs Open Radical Prostatectomy SEER (National Cancer Registry ) Database Hu JC et al, JAMA 302; 1557, 2009

50. “… (minimally-invasive surgery more likely to require salvage therapy within 6 months (27.8% v 9.1%, P < .001 )”