1. Peter Grimm, DO Seattle Prostate Institute Latest update 4/23/09

2. Problem: In the absence of randomized studies, patients, physicians, carriers, Medicare, etc: need a means to compare the effectiveness of modern treatments Purpose: The PCRSG will compare and share results for prostate cancer that are utilizable for all those who are interested 10/31/20132

3. Ignace Billiet,MD Europe David Bostwick, MD Bostwick Laboratories David Crawford, MD Univ Colorado Peter Grimm, DO Seattle Jos Immerzeel, Netherlands Mira Keyes, MD BC Cancer Agency Kupelian, Patrick, MD MD Anderson Orlando Robert Lee Duke University Medical Center Brian Moran, MD Chicago Prostate Institute Greg Merrick, MD Schiffler Cancer Center Jeremy Millar, MD Australia Mack Roach, MD UCSF Richard Stock, MD Mt. Sinai New York 10/31/20133

4. Katsuto Shinohara, MD UCSF John Sylvester, MD SPI Mark Scholz, MD Prostate Cancer Research Institute Ed Weber, MD SPI Anthony Zietman, MD Harvard Joint Center Michael Zelefsky, MD Memorial Sloan Kettering Fellows Jason Wong, MD Residents: Jyoti Mayadev, MD University of Washington Stacy Wentworth, MD Wake forest Robyn Vera, DO Medical College of Virginia 10/31/20134

5. Study >15,000 articles reviewed from 2000-2009 Pub Med, Medline, Google Scholar, Elsevier search 603 Treatment Results Articles Identified Expert Panel Established Criteria for Inclusion Treatment Articles screened for study group criteria

6. 1.Patients must be stratified into recognizable Pre-Treatment Risk groups: Low, Intermediate, and High Risk by either DAmico, Zelefsky or NCCN stratification 2.bRFS standard endpoint ASTRO, Phoenix, and PSA < 0.2 (surgery) 3.Clinical Staging No exclusions: i.e. No Pathologic staging 4.EBRT must be minimum 72 Gy IMRT / conformal 10/31/20136

7. 5.All Treatment modalities considered: Seeds, Surgery, IMRT, HIFU, CRYO Protons, HDR 6.Accepted results: Peer Reviewed Journals Only 7.Low Risk Accepted minimum number 100 pts 8.Int Risk Accepted minimum number 100 pts 9.High Risk Accepted minimum number 50 pts 10.Minimum median F/U : 5 yr 10/31/20137

8. RP EBRTCryoBrachyRobot RP ProtonHIFU 15/2067/1652/2620/1570/531/90/27 7%4%8%13%0%11%0% Total 603 Treatment Articles. Some articles addressed several treatments 10/31/20138

9. 7 7 5 5 22 16 Years CRYO Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 3 3 13 12 24 14 8 8 No TX 2 2 23 HIFU % PSA Progression Free 20 11 15 Protons 21 4 4 18 17 19 9 9 10 EBRT & Seeds 13 25 Robot RP 26 10/31/20139

10. 7 7 5 5 22 16 Years CRYO Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 3 3 13 12 24 14 8 8 No TX 2 2 23 HIFU % PSA Progression Free 20 11 15 Protons 21 4 4 18 17 19 9 9 10 EBRT & Seeds 13 25 Robot RP 26 Low Risk PCSG Criteria 10/31/201310 Brachy Surgery EBRT

11. 10/31/201311

12. 5 5 41 49 43 16 52 50 51 3 3 13 12 1 1 45 7 7 47 45 14 23 8 8 2 2 22 % Progression Free 46 11 15 58 57 46 4 4 59 60 48 21 18 17 54 19 9 9 10 44 47 55 63 62 24 56 61 65 26 66 67 CRYO No TX HIFU Protons EBRT & Seeds Robot RP 62 Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201312 25

13. 5 5 41 49 43 16 52 50 51 3 3 13 12 1 1 45 7 7 47 45 14 23 8 8 2 2 22 % Progression Free 46 11 15 58 57 46 4 4 59 60 48 21 18 17 54 19 9 9 10 44 47 55 63 62 24 56 61 65 26 66 67 CRYO No TX HIFU Protons EBRT & Seeds Robot RP 62 Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references Brachy EBRT Surgery 10/31/201313 25

14. 29 30 23 16 21 5 5 26 27 19 31 6 6 % PSA Progression Free 18 12 28 3 3 17 7 7 32 14 33 9 9 8 8 2 2 25 35 34 1 1 13 Protons EBRT & Seeds HDR Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201314 15 4 4 36

15. 29 30 23 16 21 5 5 26 27 19 31 6 6 % PSA Progression Free 18 12 28 3 3 17 7 7 32 14 33 9 9 8 8 2 2 25 35 34 1 1 13 Protons EBRT & Seeds HDR Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201315 4 4 36 Brachy EBRT Surgery

16. 55 33 29 30 23 16 21 5 51 26 27 19 72 13 67 31 6 6 1 1 %PSA Progression Free 12 61 28 3 3 53 17 60 7 59 56 57 73 14 54 9 9 8 8 2 25 4 15 52 58 62 63 3 3 32 65 4 68 69 70 71 64 34 35 48 74 75 76 77 36 80 78 Protons EBRT & Seeds HDR 79 Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201316 18

17. 55 33 29 30 23 16 21 5 51 26 27 19 72 13 67 31 6 6 1 1 %PSA Progression Free 18 12 61 28 3 3 53 17 60 7 59 56 57 73 14 54 9 9 8 8 2 25 4 15 52 58 62 63 3 3 32 65 4 68 69 70 71 64 34 35 48 75 76 77 36 80 78 Protons EBRT & Seeds HDR 79 Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201317 Brachy EBRT Surgery 74

18. 6 6 11 36 13 3 3 25 15 5 5 31 EBRT Seeds + ADT 19 23 30 16 10 20 18 33 29 7 7 % PSA Progression Free 4 4 17 32 14 21 8 8 2 2 1 1 9 9 22 24 26 27 28 34 37 38 39 41 37 41 12 Protons EBRT & Seeds HDR EBRT & ADT Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201318

19. 6 6 11 36 3 3 25 15 31 EBRT Seeds + ADT 19 30 16 10 18 33 29 7 7 % PSA Progression Free 4 4 17 14 21 8 8 2 2 1 1 9 9 22 24 28 34 37 38 39 41 37 41 12 Protons EBRT & Seeds HDR EBRT & ADT Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201319 Brachy EBRT Surgery 13 32 5 5 26 20 23 27

20. 53 64 6 6 11 36 13 57 3 3 25 15 5 5 56 31 60 16 23 30 55 59 18 20 19 33 29 7 7 % PSA Progression Free 4 4 17 32 72 50 61 14 21 8 8 62 12 58 2 2 1 1 9 9 22 24 26 27 28 34 37 38 39 51 52 54 63 65 66 67 68 69 70 Seeds + HT 40 76 73 74 75 71 77 78 79 80 81 82 83 84 41 85 37 41 10 EBRT Seeds + ADT EBRT & Seeds HDR EBRT & ADT Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201320

21. 53 64 6 6 11 36 13 57 3 3 25 15 5 5 56 31 60 16 23 30 55 59 18 20 19 33 29 7 7 % PSA Progression Free 4 4 17 32 72 50 61 14 21 8 8 62 12 58 2 2 1 1 9 9 22 26 27 28 34 37 39 51 52 54 63 65 66 67 68 69 70 Seeds + HT 40 76 74 75 71 78 79 80 81 82 83 84 41 85 41 10 EBRT Seeds + ADT EBRT & Seeds HDR EBRT & ADT Years Prostate Cancer Results Study Group 3/31/09 Numbers within symbols refer to references 10/31/201321 Brachy EBRT Surgery 24 37 38 73 77

22. No Randomized studies to date By BRFS control criteria Brachytherapy alone or Comb appears superior in all risk groups Prostate studies to date rarely include Pre- treatment Risk Group stratification, confounding comparisons Only a small % of studies to date conform to basic reporting criteria 10/31/201322

23. 1-877-773-0622 www.studymanager.com 10/31/201323

24. 10/31/201324