1. Newly-Diagnosed Prostate Cancer Mark Scholz MD Prostate Oncology Specialists

2. The PSA Net

4. Types of Things We Find in the PSA Net BPH BPH Recent sexual activity Recent sexual activity Lab errors Lab errors Prostate infections Prostate infections High-Grade prostate cancer High-Grade prostate cancer Low-Grade prostate cancer Low-Grade prostate cancer

5. Annual Age-Adjusted Cancer Incidence Rates Among Males for Selected Cancers, 1975-2002 Adapted from Jemal A, et al. CA Cancer J Clin. 2006;56:106-130. Year of Diagnosis Rate per 100,000 Population 2002 260 140 160 180 200 220 240 100 120 Lung and Bronchus Colon and Rectum 80 0 20 40 60 1993 1975 1985 1983 1981197919771991 1989 198719991997 1995 2001 Prostate Urinary Bladder Non-Hodgkin Lymphoma Melanoma of the Skin PSA Testing Started 1987

6. Epidemic Prostate “Cancer” Prior to PSA (1987) 1 of 41 men died of PC (2.4%) Prior to PSA (1987) 1 of 41 men died of PC (2.4%) In 2009, with screening and early treatment, the risk of dying from PC is 1 of 53 (1.9%) In 2009, with screening and early treatment, the risk of dying from PC is 1 of 53 (1.9%) However: However: –200,000 diagnosed annually instead of 90,000 –1.5 million men are biopsied annually –The lifetime risk of biopsy is 1 out of 2

7. “Six-Core” Biopsy of 3000 Men Age 55-75 with Normal PSA PSA LevelCancer Diagnosis Rate PSA LevelCancer Diagnosis Rate 1 – 2 17% 2 – 3 24% 3 – 4 27%

8. prostate cancer radical prostatectomy specimen transition zone peripheral zone urethra

9. Prostate Biopsy Posterior View Prostate Points of needle entry

10. Tests to Detect Prostate Cancer –PSA blood test –PCA-3 urine test –Digital rectal examination –Ultrasound and MRI scans

11. “Risk of Biopsy-Detectable Prostate Cancer” Age 55 Age 55 BMI (are you fat?)22.5 BMI (are you fat?)22.5 RaceNot African American RaceNot African American PSA2.0 PSA2.0 Rectal examnormal Rectal examnormal PCA-3not done PCA-3not done Risk of any prostate Cancer = 23% Risk of High-Grade prostate cancer = 2.5%

12. Prostate Cancer Types Growth rate Growth rate Ability to spread Ability to spread

13. “Gleason” Grading of Prostate Cancer Low grade (3) Low grade (3) Higher Grade (4) Higher Grade (4) Highest Grade (5) Highest Grade (5) Score = “Adding Up” two grades Score = “Adding Up” two grades

14. Staging RiskGleasonPSA Digital Digital Low (all) < 7 < 10 Normal Intermediate (any) 710-20Nodule High (any) > 7 > 20 Mass

15. Low = Monitor Low = Monitor Intermediate = Seeds, Surgery or IMRT Intermediate = Seeds, Surgery or IMRT High-Risk = IMRT with Hormone Blockade High-Risk = IMRT with Hormone Blockade Risk Status

16. Treatment Selection Flow Chart Determine Disease Risk Intermediate High-Risk Seeds or IMRT or Cryotherapy or Surgery or Hormones or Active Surveillance or IMRT plus Short-Term Hormones Low-Risk Active Surveillance Long-Term Hormones plus IMRT plus Seeds

17. 10-Year Survival by Risk Category Low More than 100% Low More than 100% Brenner: Journal of Clinical Oncology 2005 Brenner: Journal of Clinical Oncology 2005 Intermediate With treatment 98% Intermediate With treatment 98% Mayo Clinic Journal of Urology 2008 High Surgery 95% High Surgery 95% Mayo Clinic Journal of Urology 2008 Mayo Clinic Journal of Urology 2008 Very High Early Hormone blockade: 87% Late Hormone blockade: 59% Very High Early Hormone blockade: 87% Late Hormone blockade: 59% Messing: New England Journal Medicine 1999 Messing: New England Journal Medicine 1999

18. Prostate Snatchers

19. The Prostate is “Built In”

20. Collateral Damage Loss of Sexual and Urinary Function

21. Impotence Five Years after Surgery: 1288 Men David Penson Journal of Urology 2005 Impotence Five Years after Surgery: 1288 Men David Penson Journal of Urology 2005 Incapable of an erection adequate for intercourse with Viagra Incapable of an erection adequate for intercourse with Viagra Age < 54 39% 55-59 51% 60-6456% > 65 82%

22. Surgeon 12 mo Pat Walsh(Open)93% Ahlering(Robotic)94% Shalhav(Robotic)84% Lee(Robotic)90% Urinary Continence

23. “Optimal Surgical Competency Requires a minimum of 250 Practice Cases” In the New York during the whole of the years in 2005: In the New York during the whole of the years in 2005: –25% of the urologists did a single radical prostectomy –80% of the urologists did <10 cases Savage & Vickers, Memorial Sloan Kettering Journal of Urology December 2009

24. Radiation

27. Implant Procedure

29. X-Ray of Seed Implant

30. Robotic Prostatectomy  Computer enhanced  Surgeon operates at the console within a 3D view  Bedside surgical assistant is next to the patient  Instruments move like a human wrist ( ↑ dexterity and precision)

31.  The surgeon’s hands are placed in special devices that direct the instrument movement The Surgeon Directs The Instruments

32. Standard Surgery Robotic Surgery Robotic Prostatectomy: Difference Big, Ugly Scar little, tiny scars

33. Robotic vs. Standard Prostatectomy in 2700 Patients Good: Good: –Shorter hospital stays (1.4 vs. 4.4 days) –Slightly less complications (30 vs. 36%) Not so Good: Not so Good: –Higher likelihood of needing salvage radiation therapy (28 vs 9%) –More urethral strictures (40% more likely) Hu, Jim et al. Journal of Clinical Oncology, May 2008

34. Cure Rates: Surgery vs. Seeds Cure Rates: Surgery vs. Seeds 15,000 studies reviewed 15,000 studies reviewed Expert panel determined inclusion criteria Expert panel determined inclusion criteria 603 studies met criteria 603 studies met criteria

35. Criteria for the Study Inclusion 1.Patients divided into low, intermediate & high-risk groups 2.Standardized PSA endpoints such as ASTRO, Phoenix, and PSA < 0.2 (surgery)

36. Intermediate Risk: Percentage Progression Free 8 8 12 1 22 15 23 % Progression Free Years 2 16 24 17 31 32 34 36 37 4 Brachy Surgery 40 43

37. Side Effects Comparison of: Surgery, Brachytherapy and Beam Radiation Talcott, Journal of Clinical Oncology, 2003 Talcott, Journal of Clinical Oncology, 2003

38. Quality of Life Prospective study at MGH and Harvard Prospective study at MGH and Harvard Questionnaire prior, 3, 12, 24, 36 mo. post Rx. Questionnaire prior, 3, 12, 24, 36 mo. post Rx. 522 pts treated with, IMRT, Surgery or 522 pts treated with, IMRT, Surgery or Average age: Surgery patients younger than Brachytherapy patients, who were younger than IMRT patients Average age: Surgery patients younger than Brachytherapy patients, who were younger than IMRT patients

39. Urinary Obstruction/Irritation (Higher score = worse function)

40. Incontinence

41. Bowel Problems (Higher score = worse function)

42. Sexual Dysfunction (Higher score = worse function)

43. Health Related Quality Of Life Validated Instrument Studies ~ 4230 patients in 7 studies c omparing surgery, IMRT and brachytherapy: ~ 4230 patients in 7 studies c omparing surgery, IMRT and brachytherapy: Davis JW, et al. J Urol. 2001;166:947-952 Davis JW, et al. J Urol. 2001;166:947-952 Wei JT, et al. J Clin Oncol. 2002;20:557-566 Wei JT, et al. J Clin Oncol. 2002;20:557-566 Lee WR, et al. IJROBP. 2001;51:614-623 Lee WR, et al. IJROBP. 2001;51:614-623 Talcott JA et al. JCO 2003; 21(21): 3979 Talcott JA et al. JCO 2003; 21(21): 3979 Miller DC et al. JCO 2005; 23 (12):2772 Miller DC et al. JCO 2005; 23 (12):2772 Frank SJ et al. J Urol 2007; 177: 2151 Frank SJ et al. J Urol 2007; 177: 2151 Sanda MG et al. NEJM 2008; 358(12):1250 Sanda MG et al. NEJM 2008; 358(12):1250

44. Summary Treatment Side Effects of the Seven Studies Seed implants result in: Seed implants result in: – less incontinence than surgery – more urinary symptoms like urgency or frequency – Better potency than surgery

45. Risks for Men with Low-Risk Prostate Cancer Unskillful or unnecessary therapy Unskillful or unnecessary therapy Inaccurate staging Inaccurate staging “Either this is the wrong chart or —lets just hope this is the wrong chart”

46. 77777777 777777 777 “Because of your age, I’m going to recommend doing nothing.”

47. Active Surveillance = Watchful Waiting Active Surveillance Watchful Waiting Aim Individualize therapy Avoid treatment AgeAny Older or sicker MonitoringAggressiveLax Treatment timing EarlyLate Indications for treatment PSA increase, changes on ultrasound or biopsy Cancer symptoms such as bone pain Treatment intent Cure Symptom control

48. Surgery Vs. “Watching” Bill-Axelson, New England Journal Medicine Randomized prospective trial 695 men Randomized prospective trial 695 men Mean PSA 12.8 Mean PSA 12.8 75% stage B (palpable nodule) 75% stage B (palpable nodule) 25% Gleason 7 (6% with Gleason >8) 25% Gleason 7 (6% with Gleason >8) Cancer detected by DRE, not PSA Cancer detected by DRE, not PSA

49. Bill-Axelson: 10-Year Results Surgery “ Watching” Risk Reduction CancerSurvival90%85%5%

50. Benefit of Surgery Compared to Doing Nothing at All Intermediate risk or High Risk disease Intermediate risk or High Risk disease “Watching” not Active Surveillance “Watching” not Active Surveillance No early treatment for a rising PSA No early treatment for a rising PSA 20 men operated to save 1 life 10 years later =

51. Projected Outcome in Low-Risk Disease on Active Surveillance Journal of Clinical Oncology 2005 Grade 6 Grade 6 Rectal exam normal Rectal exam normal PSA < 10 PSA < 10 Cancer in <1/3 of cores Cancer in <1/3 of cores Early treatment Early treatment 100 men Operated to Save 1 Life 10 Years in the Future =

52. Active Surveillance Delaying curative therapy until evidence of cancer growth at which time curative treatment is administered

53. Active Surveillance in 450 Men with Low to Intermediate Risk Disease Klotz—Journal of Clinical Oncology 2010 Surveillance Surveillance –PSA and DRE every 3 months –Biopsy every 2-4 years Progression Progression –Increase in Gleason score –PSA doubling in less than 3 years –New or enlarging nodule on rectal examination

54. Results Ten Years Patients: Patients: –Average age 70 –71% “Low Risk” 83% Gleason 3+3, 17% Gleason 3+4 83% Gleason 3+3, 17% Gleason 3+4 85% PSA < 10, 12% PSA 10-15 85% PSA < 10, 12% PSA 10-15 10-year overall survival was 68% 10-year overall survival was 68% –97 died of causes besides prostate cancer –5 died of prostate cancer

55. Enhancement of Active Surveillance Biopsy showing < 1/3 cores positive Biopsy showing < 1/3 cores positive Color doppler ultrasound every 6 months Color doppler ultrasound every 6 months Multi-Phasic MRI annually Multi-Phasic MRI annually Proscar or Avodart Proscar or Avodart

56. Color Doppler Ultrasound Identifies lesions for monitoring Identifies lesions for monitoring Measures tumor progression Measures tumor progression

57. Color Doppler Image

58. Six Months Earlier

59. 3-Tesla Prostate MRI Anatomy Blood flow Chemical concentrations Cellular density

60. Proscar and Avodart Inhibit cancer Inhibit cancer Improve PSA accuracy Improve PSA accuracy Increase biopsy accuracy Increase biopsy accuracy Improve urination Improve urination Grow hair Grow hair Lower libido Lower libido Breast growth Breast growth AdvantagesSide Effects

61. Conclusions: Active Surveillance Aggressive, hurried prostate cancer treatment benefits very, very few men Aggressive, hurried prostate cancer treatment benefits very, very few men The window of opportunity to defeat early-stage disease is measured in years, not months The window of opportunity to defeat early-stage disease is measured in years, not months Active surveillance rather than immediate radical treatment allows men with low-risk disease to avoid the side effects of treatment for many years if not indefinitely. Active surveillance rather than immediate radical treatment allows men with low-risk disease to avoid the side effects of treatment for many years if not indefinitely.