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Comparing Treatment Results Of PROSTATE CANCER Prostate Cancer Results Study Group - Version: 15_01_2013(3) Peter Grimm, DO Prostate Cancer Center of Seattle 15_01_2013(3) 1 Problem: Patients, physicians and carriers need a simple, unbiased means to compare the cancer control rates of modern prostate cancer treatment methods. 15_01_2013(3) 2 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 15_01_2013(3) 3 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 15_01_2013(3) 4 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 15_01_2013(3) 5 ABOUT THIS REVIEW STUDY 23,000+ prostate studies were published between 2000 and 2012 989 of those studies featured treatment results 195 of those met the criteria to be included in this review study. (*1 & 2 group) Some treatment methods are underrepresented due to failure to meet criteria st 15_01_2013(3) nd 6 “Will I be cured?” or “Will my treatment make me cancer free?” are valid patient questions. However, PSA values (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. 15_01_2013(3) 7 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. 15_01_2013(3) 8 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 15_01_2013(3) 9 Criteria for Inclusion of Article* 1. Patients should be separated into Low, Intermediate, and High Risk 2. Success must be determined by PSA analysis 3. 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) 4. Article must be in a Peer Reviewed Journal * Expert panel consensus 15_01_2013(3) 10 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: [email protected] 15_01_2013(3) 11 RP EBRT/ IMRT Cryo Brachy/ HDR Robot RP Proton HIFU 8.7% 10.6% 6% 19% 6% 23% 3% 25/285 28/263 2/33 51/275 4/65 3/13 1/33 Total of 989 Treatment Articles. Some articles addressed several treatments and were counted as separate articles for each treatment. *A few articles evaluated other/minor treatments and are not listed here. These calculations only include primary accepted articles, and do not include secondary acceptance totals. 15_01_2013(3) 12 How to Interpret the Results Each treatment is given a symbol. For example Seed implant alone (Brachy) is given a blue dot with a number in it.27 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 15_01_2013(3) 13 How to Interpret the Results 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 published Treatment Success % would fit on this plot. *Next Slide 15_01_2013(3) 14 Low Risk Stage: T1 or T2a,b Gleason Sum < 6 PSA < 10 ng/ml 15_01_2013(3) 15 % PSA Progression Free Treatment Success LOW RISK RESULTS 100 23 25 4 22 30 6 37 3 33 29 101 31 90 19 14 21 13 8 24 38 39103 18 102 2 26 40 1 100 7 27 35 17 32 10 28 36 12 107 106 9 80 EBRT & Seeds 5 16 104 108 15 Robot RP Seeds Surgery EBRT CRYO HIFU 70 34 ← Years from Treatment → 60 Protons HDR 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 16 LOW RISK RESULTS % PSA Progression Free Treatment Success Weighted Brachy 100 EBRT 23 25 4 22 30 6 37 3 31 90 19 14 21 13 8 24 33 29 101 39103 18 102 38 40 1 100 2 26 7 27 35 17 32 10 28 36 5 16 12 107 106 104 9 80 108 15 Surgery 70 34 ← Years from Treatment → 60 EBRT & Seeds Robot RP Seeds Surgery EBRT CRYO HIFU Protons HDR 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 17 “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?” 15_01_2013(3) 18 LOW RISK RESULTS % PSA Progression Free Treatment Success >40 months follow-up or less than 100 patients 100 68 51 50 97 96 23 46 14 21 66 25 22 8 13 48 4 8175 62 37 35 44 86 17 3069641 3 60 82 33 32 71 85 1067 9865 3172 99 29 101 39103 28 94 8489 95 42 61 93 18 88 102 38 54 36 73 1947 24 43 55 78 2 26 64 12 83 40 58 1 100 7 87 76 56 107 106 77 9 70 80 41 15 45 57 74 79 59 90 53 90 80 + 27 5 16 52 104 108 34 ← Years from Treatment → 91 60 1 15_01_2013(3) Seeds Surgery EBRT CRYO HIFU 63 70 Seeds & ADT EBRT & ADT EBRT & Seeds Robot RP 49 11 2 3 4 5 6 7 8 9 10 11 12 13 14 15 • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle Protons Hypo EBRT HDR 19 LOW RISK RESULTS Weighted % PSA Progression Free Treatment Success >40 months follow-up or less than 100 patients 100 EBRT Brachy 68 51 50 92 96 23 46 14 21 97 66 25 22 8 13 48 4 8175 62 37 35 44 86 17 3069641 3 60 82 33 32 71 85 1067 39103 65 28 94 98 84893172 99 29 101 95 42 61 93 18 88102 38 54 36 73 1947 24 43 55 78 2 26 64 12 83 40 58 1 100 7 87 76 56 107 106 77 9 70 80 41 15 45 57 74 79 59 90 53 90 80 + 27 5 16 52 104 108 Surgery 63 70 34 ← Years from Treatment → 91 60 49 11 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 • Prostate Cancer Results Study Group Seeds & ADT EBRT & ADT EBRT & Seeds Robot RP Seeds Surgery EBRT CRYO HIFU Protons Hypo EBRT HDR • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 20 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 15_01_2013(3) 21 % PSA Progression Free Treatment Success INTERMEDIATE RISK RESULTS 100 33 14 24 2313 35 49 151 90 16 4 38 31 42 3 40 32 Seeds + ADT EBRT & Seeds 39 6 12 43 18 28 9 26 25 29 41 1 8 10 11 19 5 7 70 + 34 15 44 30 36 45 80 Robot RP 37 60 Hypo EBRT 17 27 150 48 2 46 20 Brachy Seeds Alone Surgery EBRT CRYO HIFU HDR 50 ← Years from Treatment → 40 EBRT, Seeds + ADT 21 22 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Protons • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 22 INTERMEDIATE RISK RESULTS % PSA Progression Free Treatment Success Weighted EBRT & Seeds Brachy 100 33 14 24 2313 35 49 151 90 16 4 38 31 42 3 40 32 43 18 28 9 26 25 29 41 1 8 10 11 19 5 7 60 EBRT 20 Hypo EBRT 17 27 150 48 2 46 Surgery 50 ← Years from Treatment → 40 15_01_2013(3) 2 3 4 5 6 21 7 8 Brachy Seeds Alone Surgery EBRT CRYO HIFU HDR EBRT, Seeds + ADT 22 1 Seeds + ADT EBRT & Seeds 39 6 12 70 + 34 15 44 30 36 45 80 Robot RP 37 9 10 11 12 13 14 15 Protons • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle 23 INTERMEDIATE RISK RESULTS % PSA Progression Free Treatment Success >40 months follow-up or less than 100 patients 100 10459 EBRT + ADT 54 56 33 59 55 66 24 23 13 14 35 79 49 59 92 98 151 34 1544 96 4 57 16 38 58 68 69 1093036 45 10599 77 12 39 83 107 82 97 6106 42 73 3191 108 51 3 72 62 18 6393 43 71 86 81 95 28 74 67 50 150 90 5 92652 19 65 78 70 7 25 103 29 76 102 41 1 60100 48 8 87 85 88 53 2 10101 11 75 46 84 90 80 70 60 89 94 Robot RP 37 + 40 EBRT & Seeds 32 17 27 Seeds + ADT 64 20 Hypo EBRT Brachy Seeds Alone Surgery EBRT CRYO HIFU HDR 50 ← Years from Treatment → 40 21 80 1 15_01_2013(3) 2 3 4 5 EBRT, Seeds + ADT 22 6 7 8 9 10 11 12 13 14 15 Protons • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle 24 INTERMEDIATE RISK RESULTS weighted Treatment Success % PSA Progression Free >40 months follow-up or less than 100 patients Brachy 100 10459 33 66 55 24 23 13 14 35 79 49 92 98 151 34 1544 96 4 57 16 38 58 68 69 30 36 45 109 99 77 39 83 105 82 107 97 612 42 73 31 91 108 51 106 3 72 62 18 6393 43 71 86 81 95 28 74 67 50 150 90 5 92652 19 65 78 70 7 25 103 29 76 102 41 1 60100 48 8 87 85 88 53 2 10101 11 75 46 84 Robot RP 37 EBRT 90 80 70 60 89 94 20 + 40 32 17 27 64 Surgery 50 ← Years from Treatment → 40 15_01_2013(3) 2 3 4 5 22 6 7 8 Seeds + ADT EBRT & Seeds Hypo EBRT Brachy Seeds Alone Surgery EBRT CRYO HIFU HDR EBRT, Seeds + ADT 21 80 1 EBRT + ADT 54 56 9 10 11 12 13 14 15 Protons • Prostate Cancer Results Study Group • Numbers within symbols refer to references Prostate Cancer Center of Seattle 25 Zelefsky definition 2 or more factors Gleason > 7 PSA 10-20 Clinical Stage T1c- T2b D'Amico Gleason Score 8-10 PSA >20 15_01_2013(3) 26 % PSA Progression Free Treatment Success HIGH RISK RESULTS 20 19 18 3 8 16 45 109 112 4 108 Surg & ADT EBRT & ADT 17 40 3 34 9 41 13 36 25 101 113 106 118 EBRT & Seed 112 44 43 32 2 48 1 33 111 21 10 114 12 14 46 28 42 8 110 31 Hypo EBRT 104 24 5 12139 119 115 11 26 76 103 35 37 47 117 Protons HDR 3011627 107 102 15 105 23 29 ← Years from Treatment → 49 EBRT Seeds + ADT Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 27 HIGH RISK RESULTS % PSA Progression Free Treatment Success Weighted EBRT, Seeds & ADT 20 Brachy 16 109 45 19 18 3 22 8 112 4 Surg & ADT EBRT & ADT 108 17 40 3 34 9 41 13 36 25 101 113 106 118 EBRT EBRT & Seeds 112 44 43 32 2 48 1 33 111 21 10 114 12 14 28 42 8 110 46 31 Hypo EBRT 104 24 5 12139 119 115 11 26 76 103 35 37 47 117 Surgery 3011627 107 102 15 105 HDR 23 29 ← Years from Treatment → Protons 49 EBRT Seeds + ADT Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) Prostate Cancer Center of Seattle 28 HIGH RISK RESULTS % PSA Progression Free Treatment Success >40 months follow-up or less than 100 patients 92 65 81 20 19 18 80 74 78 67 55 40 75 3 85 60 72 54 34 91 66 41 9 7968 71 136436 50 53 25 101 23 62113 106 118 ← Years → 3 22 8 1645 109 112 4 108 Surg & ADT EBRT & ADT 17 4376 EBRT & Seed 112 57 48 59 10 42 56 1 12 114 8 61 90 110 89 33 111 5 21 14 39 121 70 119 119 11 115 103 83 7 8226 6 35 52 63 84 116 73 31 58 27 77 46 107 86 87 88 102 15 105 51 29 from 69 Treatment 2 28 Hypo EBRT 104 24 117 Protons 30 49 HDR EBRT Seeds + ADT Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) 37 47 32 44 Prostate Cancer Center of Seattle HIFU 29 HIGH RISK RESULTS Weighted >40 months follow-up or less than 100 patients % PSA Progression Free Treatment Success Brachy 92 65 81 20 19 18 80 74 78 67 4075 3 85 60 72 54 91 66 34 941 68 71 13643679 50 53 25 101 113 62 106 118 3 22 8 16 45 109 112 4 108 Surg & ADT EBRT & ADT 17 55 4376 EBRT & Seed 112 57 48 59 10 114 42 56 1 12 8 61 90 110 89 33 111 5 21 14 39 119 70 11 115 103 83 7 8226 35 6 52 63 84 73 31 30116 58 27 77 46 107 86 87 88 102 15 105 51 23 29 from 69 Treatment 2 28 Hypo EBRT 104 24 EBRT ← Years → Protons HDR Surgery 49 EBRT Seeds + ADT Robot RP • Prostate Cancer Results Study Group • Numbers within symbols refer to references 15_01_2013(3) 37 47 32 44 Prostate Cancer Center of Seattle HIFU 30 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 15_01_2013(3) 31 = 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 15_01_2013(3) 32 + = “CRYO” Cryo Therapy = EBRT, Seeds, & ADT = Seeds & ADT = EBRT & ADT = Surgery & ADT = “Brachy” = all seed implant treatments = all Surgery treatments = all EBRT treatments = all EBRT & Seeds = all EBRT, Seeds & ADT 15_01_2013(3) 33 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 15_01_2013(3) 34 Peter Grimm, DO [email protected] Lisa Grimm, Research Coordinator [email protected] Or ProstateCancerTC.com Or contact PCRSG member Prostate Cancer Center of Seattle website www.Prostatecancertreatmentcenter.com 15_01_2013(3) 35