Peter Grimm, DO Prostate Cancer Center of Seattle

1. Peter Grimm, DO Prostate Cancer Center of Seattle Comparing Treatment Results Of PROSTATE CANCER Prostate Cancer Results Study Group 2012

2. Prostate Cancer Results Study Group Problem: Patients need a simple means to compare the cancer control rates of modern prostate cancer treatment methods. 1/2/2020 2

3. Prostate Cancer Results Study Group To solve this problem, we have assembled experts from key treating disciplines: Surgery, External Radiation, Internal (or Brachytherapy), High Frequency Ultrasound, and Proton Therapy The purpose of this work is to do a complete review study of the current literature on prostate cancer treatment 1/2/2020

4. Prostate Cancer Results Study Group Ignace Billiet, MD F.E.B.U., Urologist Kortrijk, Belgium David Bostwick, MD Bostwick Laboratories David Crawford, MD Univ Colorado, Denver Adam Dicker, MD Thomas Jefferson U Philadelphia,PA Steven Frank, MD MD Andersen, Houston Texas Peter Grimm, DO Prostate Cancer Center of Seattle Jos Immerzeel, MD De Prostaat Kliniek Netherlands Stephen Langley, MD St Luke's Cancer Centre, Guildford England Alvaro Martinez, MD William Beaumont , Royal Oak, Mi Mira Keyes, MD BC Cancer Agency , Vancouver Canada Patrick Kupelian, MD UCLA Med Center Los Angeles Robert Lee , MD Duke University Medical Center Stefan Machtens, MD University Bergisch, Gladbach Germany Jyoti Mayadev, UC Davis Davis ,California Brian Moran, MD Chicago Prostate Institute Chicago

5. Prostate Cancer Results Study Group Gregory Merrick, MD Schiffler Cancer Center Wheeling West Virginia Jeremy Millar, MD Alfred Health and Monash University, Melbourne Australia Mack Roach, MD UCSF San Francisco California Richard Stock, MD Mt. Sinai New York Katsuto Shinohara, MD UCSF San Francisco California Mark Scholz, MD Prostate Cancer Research Institute Marina del Ray California Edward Weber, MD Prostate Cancer Center of Seattle Anthony Zietman, MD Harvard Joint Center Boston Ma Michael Zelefsky, MD Memorial Sloan Kettering New York Jason Wong, MD UC Irvine Irvine California Stacy Wentworth, MD Piedmont Radiation Oncology Greensboro , NC Robyn Vera, DO Medical College of Virginia Richmond Virginia

6. 21,000+ prostate studies were published between 2000 and 2011 917 of those studies featured treatment results 145 of those met the criteria to be included in this review study. Some treatment methods are under-represented due to failure to meet criteria ABOUT THIS REVIEW STUDY

7. About This Study “Will I be cured?” or “Will my treatment make me cancer free?” are valid patient questions. However, PSA numbers (our best measurement tool today) cannot answer this absolutely. The current state-of-the-art can only indicate that the treatment was “successful” if PSA numbers do not indicate cancer progression.

8. About This Study After prostate removal, PSA numbers usually fall rapidly to very low numbers and stay low. After radiation, PSA numbers usually come down slower, might increase then fall in the 1 to 3 year range (called a “PSA Bump”), and then usually level out at a higher number than the surgery patient. These different PSA expectations result in dissimilar ways to review a man’s PSA history to judge treatment success. This study makes no attempt to standardize those evaluation systems.

9. Abbreviations Brachy = Seed implantation either permanent or temporary seeds IMRT = Intensity Modulated Radiation Therapy a form of External Radiation RP = Standard open radical prostatectomy Robot RP = Robotic Radical Prostatectomy HIFU = High frequency Ultrasound Cryo= Cryotherapy Protons = form of External Radiation using Protons EBRT= External Beam Radiation Therapy ADT= Hormone Therapy

10. Criteria for Inclusion of Article* * Expert panel consensus Patients should be separated into Low, Intermediate, and High Risk Success must be determined by PSA analysis All Treatment types considered: Seeds (Brachy), Surgery (Standard or Robotic), IMRT (Intensity Modulated Radiation), HIFU (High Frequency Ultrasound), CRYO (Cryo Therapy), Protons, HDR (High dose Rate Brachytherapy) Article must be in a Peer Reviewed Journal 1/2/2020 10

11. Criteria for Inclusion of Article (cont.) 5. Low Risk articles must have a minimum of 100 patients 6. Intermediate Risk articles must have a minimum of 100 patients 7. High Risk articles, because of fewer patients, need only 50 patients to meet criteria 8. Patients must have been followed for a median of 5 years For additional criteria information contact: lisa@prostatecancertc.com 1/2/2020 11

12. % Articles Meeting Criteria Total of 917 Treatment Articles. Some articles addressed several treatments and were counted as separate articles for each treatment. 1/2/2020 12

13. Each treatment is given a symbol. For example Seed implant alone (Brachy) is given a blue dot with a number in it. The number in the symbol refers to the article. The article can be found in the notes section below the slide ( go into “view” in up left corner of PowerPoint and click on note section, then click on this portion and scroll down to see all the references) Treatment Success % = Percent of men whose PSA numbers do not indicate cancer progression. (progression free) at a specific point in time The bottom line indicates the number years the study is out An example, the blue dot with 27 inside indicates that, as per article 27, 97% of the patients treated with seeds alone in low risk patients at 12 years were free of disease progression according to PSA numbers How to Interpret the Results 27

14. First Establish your clinical risk group* by looking at the definitions or ask your physician Refer only to those slides for your risk group Make your own judgment and then ask a doctor in each discipline ( Seeds, External Radiation Surgery, etc) to tell you where his/her own peer reviewed publishedTreatment Success % would fit on this plot. How to Interpret the Results *Next Slide

15. LOWRisk Group Definition Low Risk Stage: T1 or T2a,b Gleason Sum < 6 PSA < 10 ng/ml

16. LOW RISK RESULTS % PSA Progression Free 23 14 21 27 25 13 8 4 22 37 35 6 30 3 33 32 10 39 103 31 29 101 28 EBRT & Seeds Treatment Success 18 102 24 38 36 5 105 16 19 2 26 12 40 Robot RP 1 100 7 104 9 15 CRYO HIFU 34 Protons ← Years from Treatment → HDR 11 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

17. LOW RISK RESULTS Weighted Brachy % PSA Progression Free 23 14 21 27 EBRT 25 13 8 4 22 37 35 6 30 3 33 32 10 39 103 31 29 101 28 18 EBRT & Seeds 102 24 38 36 5 105 16 19 2 26 12 40 1 100 Robot RP 7 104 9 15 Treatment Success Surgery CRYO HIFU 34 Protons ← Years from Treatment → HDR 11 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

18. Question about the Criteria “The PCRSG criteria is pretty strict and not a lot of studies fit. What happens if you include articles with only 40 months of follow up or have a long follow up but less than 100 patients?”

19. LOW RISK RESULTS >40 months follow-up or less than 100 patients % PSA Progression Free 68 51 50 46 97 96 23 14 21 Seeds & ADT 27 66 25 + 22 13 8 48 4 75 62 37 81 44 86 35 6 30 82 3 EBRT & ADT 60 69 41 71 33 32 10 65 85 39 103 98 Treatment Success 84 31 72 29 101 28 67 89 42 94 95 61 93 18 88 EBRT& Seeds 102 24 38 73 54 36 5 105 16 19 47 78 43 2 26 12 64 55 52 40 83 58 Robot RP 1 100 87 7 76 56 104 77 9 70 80 41 15 45 57 74 79 59 53 90 CRYO 63 HIFU 34 Protons ← Years from Treatment → Hypo EBRT 91 49 HDR 11 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

20. LOW RISK RESULTS Weighted >40 months follow-up or less than 100 patients EBRT Brachy % PSA Progression Free 68 51 50 46 92 96 23 14 21 Seeds & ADT 97 27 66 25 + 22 13 8 48 4 75 62 37 81 44 86 35 6 30 82 3 EBRT & ADT 60 69 41 71 33 32 10 65 85 39 103 Treatment Success 84 31 72 29 101 28 67 98 89 42 94 95 61 93 18 88 EBRT& Seeds 102 24 38 73 54 36 5 105 16 19 47 78 43 2 26 12 64 55 52 40 83 58 Robot RP 1 100 87 7 76 56 104 77 9 70 80 41 15 45 57 74 79 59 Surgery 53 90 CRYO 63 HIFU 34 Protons ← Years from Treatment → Hypo EBRT 91 49 HDR 11 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

21. Intermediate Risk Patient Definition Zelefsky definition Only 1 factor Clinical Stage T2c Gleason score > 7 PSA > 10 ng/ml D’Amico definition PSA 10-20 Gleason Score 7 or Stage T2b

22. INTERMEDIATE RISK RESULTS % PSA Progression Free 33 24 Robot RP 13 23 37 14 35 Seeds + ADT 34 + 44 15 40 Treatment Success 16 4 32 EBRT & Seeds 38 36 45 30 39 6 12 Hypo EBRT 42 3 43 47 27 17 18 Seeds Alone 28 5 26 19 9 7 25 29 41 1 2 8 10 11 46 20 HDR EBRT, Seeds + ADT ← Years from Treatment → 21 Protons 22 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

23. INTERMEDIATE RISK RESULTS Weighted EBRT & Seeds Brachy % PSA Progression Free 33 24 Robot RP 13 23 37 14 35 Seeds + ADT 34 + 44 15 40 16 4 32 EBRT & Seeds 38 30 36 45 39 6 12 Hypo EBRT 42 3 43 47 27 17 18 Seeds Alone 28 5 26 19 9 Treatment Success 7 25 29 41 1 2 8 10 11 46 EBRT Surgery 20 HDR EBRT, Seeds + ADT ← Years from Treatment → 21 Protons 22 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

24. INTERMEDIATE RISK RESULTS >40 months follow-up or less than 100 patients % PSA Progression Free EBRT + ADT 54 56 59 104 33 24 Robot RP 13 59 66 55 23 37 14 79 35 59 92 98 Seeds + ADT 34 + 15 44 96 40 Treatment Success 57 16 4 32 EBRT & Seeds 38 30 36 68 69 58 45 99 77 105 12 39 83 82 97 6 73 Hypo EBRT 42 51 91 3 64 43 72 47 27 62 63 93 86 71 17 Seeds Alone 18 50 81 95 28 74 67 90 26 19 5 9 52 78 65 70 7 25 103 102 29 41 76 60 100 1 2 85 88 53 8 87 10 75 101 11 46 84 94 89 20 HDR EBRT, Seeds + ADT ← Years from Treatment → 21 Protons 80 22 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

25. INTERMEDIATE RISK RESULTS weighted >40 months follow-up or less than 100 patients Brachy % PSA Progression Free EBRT + ADT 54 56 59 104 33 24 Robot RP 13 66 55 23 37 14 EBRT 79 35 92 98 Seeds + ADT 34 + 15 44 96 40 EBRT & Seeds 57 16 4 32 38 36 68 69 58 30 45 99 77 12 39 83 105 82 97 6 73 Hypo EBRT 42 51 91 3 64 43 72 47 27 62 63 93 86 71 17 Seeds Alone 18 50 81 95 28 74 67 90 26 19 5 9 52 78 65 Treatment Success 70 7 25 103 102 29 41 76 60 100 1 2 85 88 53 8 87 10 75 101 11 46 84 94 Surgery 89 20 HDR EBRT, Seeds + ADT ← Years from Treatment → 21 Protons 80 22 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

26. High Risk Patient Definition Zelefsky definition 2 or more factors Gleason > 7 PSA 10-20 Clinical Stage T1c- T2b D'Amico Gleason Score 8-10 PSA >20

27. HIGH RISK RESULTS % PSA Progression Free 20 16 109 45 19 18 4 108 EBRT & ADT 38 22 Treatment Success 17 EBRT & Seeds 40 37 3 43 47 Hypo EBRT 34 32 44 2 41 104 9 28 10 48 13 36 42 24 1 12 8 25 110 101 106 5 21 33 14 39 26 11 103 7 6 35 Protons 31 30 27 46 107 HDR 15 102 105 EBRT Seeds + ADT 29 23 ← Years from Treatment → 49 Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

28. HIGH RISK RESULTS Weighted EBRT, Seeds & ADT % PSA Progression Free Brachy 20 16 109 45 19 18 4 108 EBRT & ADT 38 22 17 EBRT & Seeds 40 37 3 43 47 Hypo EBRT 34 32 44 2 41 104 9 28 10 48 13 36 42 24 1 12 8 25 Treatment Success 110 101 106 5 21 33 14 39 Surgery 26 11 EBRT 103 7 6 35 Protons 31 30 27 46 107 HDR 15 102 105 EBRT Seeds + ADT 29 23 ← Years from Treatment → 49 Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

29. HIGH RISK RESULTS >40 months follow-up or less than 100 patients % PSA Progression Free 92 65 20 16 109 81 45 19 18 80 4 108 74 EBRT & ADT 78 38 22 Treatment Success 17 67 EBRT & Seeds 55 40 75 37 3 72 85 43 76 47 Hypo EBRT 54 34 32 44 91 66 2 41 104 9 79 68 57 28 10 48 71 64 59 13 36 42 24 50 56 1 12 8 53 25 61 89 90 110 101 5 21 62 106 33 14 70 39 60 26 11 103 83 82 7 6 35 Protons 52 63 84 31 30 73 58 27 46 77 107 HDR 86 87 15 102 88 105 51 EBRT Seeds + ADT 29 23 ← Years from Treatment → 49 69 Robot RP HIFU • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

30. HIGH RISK RESULTS Weighted >40 months follow-up or less than 100 patients Brachy % PSA Progression Free 92 65 20 16 109 81 45 19 18 80 4 108 74 EBRT & ADT 78 38 22 Treatment Success 17 67 EBRT & Seeds 55 75 40 37 3 72 85 43 76 47 Hypo EBRT 54 34 32 44 91 66 2 41 104 9 79 68 57 28 10 48 71 64 59 13 36 42 24 50 56 1 12 8 53 25 61 90 89 110 101 EBRT 5 21 62 106 33 14 70 39 60 26 11 103 83 82 7 6 35 Protons 52 63 84 31 30 73 58 27 46 77 HDR 107 86 87 15 102 88 105 51 EBRT Seeds + ADT Surgery 29 23 ← Years from Treatment → 49 69 Robot RP HIFU • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle

31. OBSERVATIONS For most low risk patients, most therapies will be successful. There appears to be a higher cancer control success rate for Brachy over EBRT and Surgery for all groups. Patients are encouraged to look at graphs and determine for themselves Serious side effect rates must be considered for any treatment Relaxing the report selection criteria doesn’t seem to impact the results substantially 1/2/2020 31

32. Slide Symbols & Abbreviations = Seeds alone = EBRT & Seeds = Surgery = Standard Radical Prostatectomy = “Robot” =Robotic Prostatectomy = “HIFU” = High Frequency Ultrasound = “HDR”= High Dose Rate Brachytherapy +/-EBRT = EBRT alone = Hypo EBRT = Protons

33. Slide Symbols & Abbreviations (cont.) = “CRYO” Cryo Therapy = EBRT, Seeds, & ADT = Seeds & ADT = EBRT & ADT = “Brachy” = all seed implant treatments = all Surgery treatments = all EBRT treatments = all EBRT & Seeds = all EBRT, Seeds & ADT +

34. Risk Group Definitions Low Risk Stage: T1 or T2a,b Gleason Sum < 6 PSA < 10 ng/ml • Intermediate Risk • Stage T1 or T1-2 Stage T1-2 • Gleason Score 7 or Gleason 6 • PSA < 10 PSA 10-20 High Risk Stage T2c or T3 Gleason score ≥ 8 PSA > 20 ng/mL

35. For More Information Peter Grimm, DO peter@grimm.com Lisa Grimm, Research Coordinator lisa@prostatecancertc.com Or ProstateCancerTC.com Or contact PCRSG member Prostate Cancer Treatment Center website www.Prostatecancertreatmentcenter.com