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Peter Grimm, DO Prostate Cancer Center of Seattle

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1 Peter Grimm, DO Prostate Cancer Center of Seattle
Comparing Treatment Results Of PROSTATE CANCER Prostate Cancer Results Study Group 2013 Peter Grimm, DO Prostate Cancer Center of Seattle 3/27/2017 1

2 Prostate Cancer Results Study Group
Problem: Patients, physicians and carriers need a simple, unbiased means to compare the cancer control rates of modern prostate cancer treatment methods. 3/27/2017 3/27/2017 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 3/27/2017 3/27/2017 3

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 Brian Davis, MD Mayo Clinic Rochester, Minnesota 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 3/27/2017

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 California Robyn Vera, DO Radiant Oncology Lacey Washington 3/27/2017

6 ABOUT THIS REVIEW STUDY
25,000+ prostate studies were published between 2000 and 2012 1,066 of those studies featured treatment results 218 of those met the criteria to be included in this review study. (*1st & 2nd group) Some treatment methods are under-represented due to failure to meet criteria 3/27/2017

7 About This Study “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. 3/27/2017

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. 3/27/2017

9 Abbreviations Brachy = Seed implantation, either permanent or
temporary seeds EBRT= External Beam Radiation Therapy (includes IMRT- Intensity Modulated Radiation) RP = Standard open radical prostatectomy Robot RP = Robotic Radical Prostatectomy HIFU = High frequency Ultrasound Cryo= Cryotherapy Protons = form of External Radiation using Protons ADT= Hormone Therapy 3/27/2017

10 Criteria for Inclusion of Article*
Patients should be separated into Low, Intermediate, and High Risk groups Success must be determined by PSA analysis All Treatment types considered: Seeds (Brachy), Surgery (Standard or Robotic), EBRT (External beam radiation therapy & IMRT (Intensity Modulated Radiation therapy), HIFU (High Frequency Ultrasound), CRYO (Cryo Therapy), Protons, HDR (High dose Rate Brachytherapy) Article must be in a Peer Reviewed Journal * Expert panel consensus 3/27/2017 3/27/2017 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: 3/27/2017 3/27/2017 11

12 % Articles Meeting Criteria
RP EBRT/IMRT Cryo Brachy/HDR Robot RP Proton HIFU 9% 12% 6% 20% 25% 3% 26/303 34/284 2/34 60/299 4/70 4/16 1/36 Total of 1,066 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. 3/27/2017 3/27/2017 12

13 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. The number in the symbol refers to the article reference number. The article references can be found in the notes section below the slides (Click on the “view” tab in upper left corner of PowerPoint and select notes page, you can then scroll down to see all the references below the graphs) Treatment Success % = Percent of men, whose PSA numbers indicate no cancer progression (progression free) at a specific point in time The bottom line of the graph indicates the number of years the study is out. An example, the blue dot with #27 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 27 3/27/2017

14 How to Interpret the Results (cont.)
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 3/27/2017

15 LOW Risk Group Definition
Stage: T1 or T2a,b Gleason Sum < PSA < 10 ng/ml 3/27/2017

16 LOW RISK RESULTS % PSA Progression Free Treatment Success
113 14 25 8 110 27 13 4 22 37 6 114 35 33 32 39 10 103 31 29 101 112 28 Treatment Success 111 EBRT & Seeds 18 115 105 24 102 36 5 16 19 2 26 12 40 1 Robot RP 100 7 106 107 104 9 108 15 109 20 CRYO 1st Group References: Kupelian P, et al. Radical prostatectomy, external beam radiotherapy <72 mGy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (RP) Thames H, et al. Increasing external beam dose for T1-T2 prostate cancer: Effect on risk groups. Int J Radiat Oncol Biol Phys 2006;65(4): (Open) Martin AG, Roy J, Beaulieu L, et al. Permanent prostate implant using high activity seeds and inverse planning with fast simulated annealing algorithm: A 12-Year Canadian experience. Int J Radiat Oncol Biol Phys 2007;67(2): Potters L, et al.12-Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urology 2005;173: Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Zelefsky M, et al. Five-Year outcome of Intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;67(1):65-70. Boorjian S, et al. Mayo Clinic validation of the D'Amico risk group classification for predicting survival following radical prostatectomy. J Urology 2008;179: Critz J, et al. 10-Year disease free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation and methodology. J Urology 2004;172: Kuban D, et al. Long-Term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57(4): Weight C, et al. Limited pelvic lymph node dissection does not improve biochemical relapse free survival at 10-years after radical prostatectomy in patients with low risk prostate cancer. J Urology 2008;71(1): Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-Free Survival After Prostate Brachytherapy. J Urol 2005;66(5): Merrick G, et al. Androgen deprivation therapy does not impact cause-specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65(3):669-67 Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Community Oncology 2007;4(4): Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Zelefsky M, et al. Long-term results of conformal radiotherapy for prostate cancer: Impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 2008;71(4): Pickles T, et al. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A single-Institutional Matched Pair Analysis. Int J Radiat Oncol Biol Phys 2010; 76(1): (EBRT) Vora et al ( Mayo) Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb Morris W, et al. Population-based Study of Biochemical and Survival Outcomes After Permanenet 125I Brachytherapy for Low and Intermediate-risk Prostate Cancer. Urol 2009; 73(4); Bhatta-Dhar N, et al. No difference in 6 year biochemical failure rates with or without pelvic lymph node during radical prostatectomy in low risk patients with prostate cancer. Urology 2004;63(3): Zietman A, et al. Comparison of conventional dose vs high dose conformal radiation therapy in clinically localized Adenocarcinoma of the prostate. JAMA 2005;294(10): & Correction: JAMA 2008; 299(8): Nguyen P, et al. Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer. Cancer 2008;113(11): Taira A, et al. Natural history of clinically staged low- and intermediate risk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): Demanes J, et al. Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by Androgen deprivation. Amer J Clin Oncol 2009;32(4): Stone N, et al. Local control following permanent prostate brachytherapy: Effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys 2010;76(2): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Protons) Zeitman A, et al. Randomized trial comparing conventional dose with high dose conformal radiation therapy in early-stage Adenocarcinoma of the prostate: Long term results from proton radiation oncology group/American College of Radiology J Clin Oncol 2010;28(7): Menon M, et al. Biochemical recurrence following robot-assisted radical prostatectomy: Analysis of 1384 patients with a median 5-year follow-up. Eur Urol. 2010;58: Kane CJ, et al. Outcomes after radical prostatectomy among men who are candidates for active surveillance: Results from the SEARCH database urology. Urol 2010;76(3): Ellis R, et al. Ten year outcomes : The clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (prostascint) in a cohort diagnosed with localized prostate cancer. Int J Radiat Oncol Biol Phys 2011; 81(1): Epub date: Hinnen, K. et al. Long term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): Zelefsky et al. Comparison of Tumor Control and toxicity Outcomes of IMRT and Brachytherapy for Patients with Favorable Risk PCa J Urology 2011; 77(4): Epub date: (Seeds) Burri, R. et al. Young Men Have Equivalent Biochemical outcomes Compared With Older Men After Treatment With Brachytherapy For Prostate Cancer. Int J Radiat Oncol Biol Phys 2010; 77(5): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Seeds) 100. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (Seeds) 101. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (EBRT) 102. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Brachy) 103. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Protons) 105. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Control Ann Surg Oncol ; 104. Sylvester, J, Grimm P et at Fifteen Year Biochemical RFS CSS, OS Following I-125 Prostate Brachytherapy in Clinically localized prostate cancer Int J Radiat Oncol Biol Phys 2011;81;376-81: 106. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 107 Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 108. Mulllins, J et al. Radical prostatectomy outcome in men 65 years old or older with low risk prostate cancer. J Urol 2012;187(5): 109. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 110. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 111 Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 112. Ding , F et al Twelve Month PSA values and perineural invasion as strong independent variables of long term biochemical outcome after prostate brachytherapy IJROP 84 (4) p 962-7, 2012 113. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 114. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 115. Mullins et al ( JH) The Impact of RRProstaatectomy on cancer Control: the 30 year anniversary J Urol p HIFU 34 Protons ← Years from Treatment → HDR 11 109 Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp. 1) Update of z Prostate Cancer Center of Seattle

17 LOW RISK RESULTS Brachy % PSA Progression Free EBRT Surgery Weighted
25 110 113 14 27 13 8 4 22 37 6 114 35 33 32 10 39 103 31 29 101 112 28 111 18 115 EBRT & Seeds 105 24 102 36 5 16 19 2 26 12 40 1 100 7 106 Robot RP 107 104 9 108 Treatment Success 15 109 20 Surgery CRYO 1st Group References: Kupelian P, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (RP) Thames H, et al. Increasing external beam dose for T1-T2 prostate cancer: Effect on risk groups. Int J Radiat Oncol Biol Phys 2006;65(4): (Open) Martin AG, Roy J, Beaulieu L, et al. Permanent prostate implant using high activity seeds and inverse planning with fast simulated annealing algorithm: A 12-Year Canadian experience. Int J Radiat Oncol Biol Phys 2007;67(2): Potters L, et al.12-Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urology 2005;173: Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Zelefsky M, et al. Five-Year outcome of Intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;67(1):65-70. Boorjian S, et al. Mayo Clinic validation of the D'Amico risk group classification for predicting survival following radical prostatectomy. J Urology 2008;179: Critz J, et al. 10-Year disease free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation and methodology. J Urology 2004;172: Kuban D, et al. Long-Term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57(4): Weight C, et al. Limited pelvic lymph node dissection does not improve biochemical relapse free survival at 10-years after radical prostatectomy in patients with low risk prostate cancer. J Urology 2008;71(1): Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-Free Survival After Prostate Brachytherapy. J Urol 2005;66(5): Merrick G, et al. Androgen deprivation therapy does not impact cause-specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65(3):669-67 Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Community Oncology 2007;4(4): Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Zelefsky M, et al. Long-term results of conformal radiotherapy for prostate cancer: Impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 2008;71(4): Pickles T, et al. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A single-Institutional Matched Pair Analysis. Int J Radiat Oncol Biol Phys 2010; 76(1): (EBRT) Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb Morris W, et al. Population-based Study of Biochemical and Survival Outcomes After Permanenet 125I Brachytherapy for Low and Intermediate-risk Prostate Cancer. Urol 2009; 73(4); Bhatta-Dhar N, et al. No difference in 6 year biochemical failure rates with or without pelvic lymph node during radical prostatectomy in low risk patients with prostate cancer. Urology 2004;63(3): Zietman A, et al. Comparison of conventional dose vs high dose conformal radiation therapy in clinically localized Adenocarcinoma of the prostate. JAMA 2005;294(10): & Correction: JAMA 2008; 299(8): Nguyen P, et al. Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer. Cancer 2008;113(11): Taira A, et al. Natural history of clinically staged low- and intermediate risk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): Demanes J, et al. Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by Androgen deprivation. Amer J Clin Oncol 2009;32(4): Stone N, et al. Local control following permanent prostate brachytherapy: Effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys 2010;76(2): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Protons) Zeitman A, et al. Randomized trial comparing conventional dose with high dose conformal radiation therapy in early-stage Adenocarcinoma of the prostate: Long term results from proton radiation oncology group/American College of Radiology J Clin Oncol 2010;28(7): Menon M, et al. Biochemical recurrence following robot-assisted radical prostatectomy: Analysis of 1384 patients with a median 5-year follow-up. Eur Urol. 2010;58: Kane CJ, et al. Outcomes after radical prostatectomy among men who are candidates for active surveillance: Results from the SEARCH database urology. Urol 2010;76(3): Ellis R, et al. Ten year outcomes : The clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (prostascint) in a cohort diagnosed with localized prostate cancer. Int J Radiat Oncol Biol Phys 2011; 81(1): Epub date: Hinnen, K. et al. Long term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): Zelefsky et al. Comparison of Tumor Control and toxicity Outcomes of IMRT and Brachytherapy for Patients with Favorable Risk PCa J Urology 2011; 77(4): Epub date: (Seeds) Burri, R. et al. Young Men Have Equivalent Biochemical outcomes Compared With Older Men After Treatment With Brachytherapy For Prostate Cancer. Int J Radiat Oncol Biol Phys 2010; 77(5): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Seeds) 100. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (Seeds) 101. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (EBRT) 102. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Brachy) 103. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Protons) 105. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 104. Sylvester, J, Grimm P et at Fifteen Year Biochemical RFS CSS, OS Following I-125 Prostate Brachytherapy in Clinically localized prostate cancer Int J Radiat Oncol Biol Phys 2011;81;376-81: 106. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 107. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 108. Mullins, J et al. Radical prostatectomy outcome in men 65 years old or older with low risk prostate cancer. J Urol 2012;187(5): 109. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 110. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 111 Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 112. Ding , F et al Twelve Month PSA values and perineural invasion as strong independent variables of long term biochemical outcome after prostate brachytherapy IJROP 84 (4) p 962-7, 2012 113. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 114. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 115. Mullins et al ( JH) The Impact of RRProstaatectomy on cancer Control: the 30 year anniversary J Urol p HIFU 34 Protons ← Years from Treatment → HDR 11 Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp. 1) Update of 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?” 3/27/2017

19 >40 months follow-up or less than 100 patients
LOW RISK RESULTS >40 months follow-up or less than 100 patients % PSA Progression Free 68 51 50 46 97 96 113 14 Seeds & ADT 66 25 110 27 + 22 13 8 48 201 4 75 62 37 81 6 44 86 35 82 114 60 EBRT & ADT 69 41 71 33 32 10 98 65 85 39 103 Treatment Success 84 31 72 99 29 101 112 28 67 111 89 42 94 95 61 93 18 88 EBRT & Seeds 105 24 73 54 102 36 5 16 19 47 78 43 2 26 12 64 55 52 202 40 83 58 1 Robot RP 100 87 7 106 76 56 107 104 77 9 70 80 108 41 15 45 57 74 79 109 59 20 53 90 CRYO 1st Group References: Kupelian P, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (RP) Thames H, et al. Increasing external beam dose for T1-T2 prostate cancer: Effect on risk groups. Int J Radiat Oncol Biol Phys 2006;65(4): (Open) Martin AG, Roy J, Beaulieu L, et al. Permanent prostate implant using high activity seeds and inverse planning with fast simulated annealing algorithm: A 12-Year Canadian experience. Int J Radiat Oncol Biol Phys 2007;67(2): Potters L, et al.12-Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urology 2005;173: Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Zelefsky M, et al. Five-Year outcome of Intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;67(1):65-70. Boorjian S, et al. Mayo Clinic validation of the D'Amico risk group classification for predicting survival following radical prostatectomy. J Urology 2008;179: Critz J, et al. 10-Year disease free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation and methodology. J Urology 2004;172: Kuban D, et al. Long-Term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57(4): Weight C, et al. Limited pelvic lymph node dissection does not improve biochemical relapse free survival at 10-years after radical prostatectomy in patients with low risk prostate cancer. J Urology 2008;71(1): Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-Free Survival After Prostate Brachytherapy. J Urol 2005;66(5): Merrick G, et al. Androgen deprivation therapy does not impact cause-specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65(3):669-67 Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Community Oncology 2007;4(4): Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Zelefsky M, et al. Long-term results of conformal radiotherapy for prostate cancer: Impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 2008;71(4): Pickles T, et al. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A single-Institutional Matched Pair Analysis. Int J Radiat Oncol Biol Phys 2010; 76(1): (EBRT) Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb Morris W, et al. Population-based Study of Biochemical and Survival Outcomes After Permanent 125I Brachytherapy for Low and Intermediate-risk Prostate Cancer. Urol 2009; 73(4); Bhatta-Dhar N, et al. No difference in 6 year biochemical failure rates with or without pelvic lymph node during radical prostatectomy in low risk patients with prostate cancer. Urology 2004;63(3): Zietman A, et al. Comparison of conventional dose vs high dose conformal radiation therapy in clinically localized Adenocarcinoma of the prostate. JAMA 2005;294(10): & Correction: JAMA 2008; 299(8): Nguyen P, et al. Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer. Cancer 2008;113(11): Taira A, et al. Natural history of clinically staged low- and intermediate risk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): Demanes J, et al. Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by Androgen deprivation. Amer J Clin Oncol 2009;32(4): Stone N, et al. Local control following permanent prostate brachytherapy: Effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys 2010;76(2): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Protons) Zeitman A, et al. Randomized trial comparing conventional dose with high dose conformal radiation therapy in early-stage Adenocarcinoma of the prostate: Long term results from proton radiation oncology group/American College of Radiology J Clin Oncol 2010;28(7): Menon M, et al. Biochemical recurrence following robot-assisted radical prostatectomy: Analysis of 1384 patients with a median 5-year follow-up. Eur Urol. 2010;58: Kane CJ, et al. Outcomes after radical prostatectomy among men who are candidates for active surveillance: Results from the SEARCH database urology. Urol 2010;76(3): Ellis R, et al. Ten year outcomes : The clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (prostascint) in a cohort diagnosed with localized prostate cancer. Int J Radiat Oncol Biol Phys 2011; 81(1): Epub date: Hinnen, K. et al. Long term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): Zelefsky et al. Comparison of Tumor Control and toxicity Outcomes of IMRT and Brachytherapy for Patients with Favorable Risk PCa J Urology 2011; 77(4): Epub date: (Seeds) Burri, R. et al. Young Men Have Equivalent Biochemical outcomes Compared With Older Men After Treatment With Brachytherapy For Prostate Cancer. Int J Radiat Oncol Biol Phys 2010; 77(5): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Seeds) 100. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (Seeds) 101. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (EBRT) 102. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Brachy) 103. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Protons) 105. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 104. Sylvester, J, Grimm P et at Fifteen Year Biochemical RFS CSS, OS Following I-125 Prostate Brachytherapy in Clinically localized prostate cancer Int J Radiat Oncol Biol Phys 2011;81;376-81: 106. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 107. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 108 Mullins, J et al. Radical prostatectomy outcome in men 65 years old or older with low risk prostate cancer. J Urol 2012;187(5): 109. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 110. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 111 Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 112. Ding , F et al Twelve Month PSA values and perineural invasion as strong independent variables of long term biochemical outcome after prostate brachytherapy IJROP 84 (4) p 962-7, 2012 113. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 114. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 115. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: Blasko J, et al. Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 2000;46(4): Demanes D, et al. High-Dose-Rate Intensity-Modulated Brachytherapy with External Beam Radiotherapy for Prostate Cancer: California Endocurietherapy;s 10-Year results. Int J Radiat Oncol Bio Phys 2005;61(5): Grimm P, et al. 10-year biochemical (prostate-specific antigen) control of prostate cancer with I-125 brachytherapy. Int J Radiat Oncol Biol Phys 2001;51(1):31-40. Hernandez D, et al. Contemporary evaluation of the D'Amico risk classification of prostate cancer. J Urol 2007; 70(5): Kupelian P, et al.Improved Biochemical relapse-free survuval with increased external radiation doses in patients with localized prostate cancer: the combined experience of nine institutions in patients treated in 1994 and Int J Radiat Oncol Biol Phys 2005;61(2): Merrick G, et al. Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2005;61(1): Vora S, et al. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Bio Phys 2007;68(4): Merrick G, et al. Brachytherapy inmen aged <54 years with clinically localized prostate cancer. BJU Int 2006;98: Bahn D, et al. Targeted cryoablation of the prostate: 7 year outcome in the primary treatment of prostate cancer. Urol 2002;60(Supp 2A):3-11. Phan T, et al. High dose rate brachytherapy as a boost for the treatment of localized prostate cancer. J Urol 2007;177: Cahlon O, et al. Ultra high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys 2008;71(2): Sylvester J, et al. 15-Year biochemical relapse free survival in clinical stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience. Int J Radiat Oncol Biol Phys 2007;67(1):57-64. Higgins G, et al. Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy. Int J Radiat Oncol Biol Phys 2006;65(4): Kollmeier M, et al. Biochemical outcomes after prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality. Int J Radiat Oncol Biol Phys 2003;57(3): Stone N, et al. Customized dose prescription for permanent prostate brachytherapy: Insights from a multicenter analysis of dosimetry outcomes. Int J Radiat Oncol Biol Phys 2007;69(5): Beyer D, et al. Relative influence of Gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. Ellis R, et al. Biochemical disease-free survival rates following definitive low-dose rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. Kwok Y, et al. Risk group stratification in patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Biol Phys 2002;53(3): Blana A, et al. Eight years’ experience with high-intensity focused ultrasonography for treatment of localized prostate cancer. J Urol 2008;72(6): Lawton, C et al. Long-term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG ) Int J Radiat Oncol Bio Phys 2011;81(1):1-7. Zelefsky M, et al. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 2001;166: (81Gy) Khuntia D, et al. Recurrence free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate-specific antigen era. Cancer 2004;100(6): Blana A, et al. First Analysis of the Long-Term results with Transrectal HIFU in Patients with Localised prostate Cancer. Eurr Urology 2008;53: Henry A, et al. Outcomes following Iodine-125 monotherapy for localized prostate cancer: the results of Leeds 10-year single-center brachytherapy experience. Int J Radiat Oncol Biol Phys 2010;76(1):50-56. Aizer A, et al. Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma. Radiotherapy and Oncology 2009; 93: Gómez-Iturriaga Piña A, et al. Median 5 year Follow-up of I-125 Brachytherapy as Monotherapy in Men aged <55 Years with Favorable Prostate Cancer. J Urology 2010;75(6): & Gómez-Iturriaga Piña A, et al. Biochemical Disease-free rate toxicicty for Men treated with I-125 prostate Brachytherapy with D90> 180GY. Int J Radia Oncol Bio Phys 2010;78(2): Prada P, et al. Prostate-specific antigen relapse-free survival and side effects in 734 patients with up to 10 years of follow-up with localized prostate cancer treated by permanent Iodine-125 implants. BJU Int 2010;106(1):32-36. Rene N, et al. Hypofractionated radiotherapy for favorable risk prostate cancer. Int J Radiat Oncol Biol Phys 2010;77(3): Lawton C, et al. Results of a Phase II Trial of Transrectal Ultrasound-guided permanent radioactive implantation of the prostate for definitive management of localized adenocarcinoma of the prostate (radiation therapy oncology group 98-05). Int J Radiat Oncol Bio Phys 2007;67(1):39-47. Deger S, et al. High dose rate (HDR) brachytherapy with conformal radiation therapy for localized prostate cancer. Eurr Urology 2005;47(4): Colberg J, et al. Surgery versus implant for early prostate cancer: results from a single institution, Cancer J 2007;13(4): (RP) Colberg J, et al. Surgery versus implant for early prostate cancer: results from a single institution, Cancer J 2007;13(4): (Seeds) D’Amico A, et al. Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 2002;95(2): (RP) D’Amico A, et al. Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 2002;95(2): (EBRT) Block T, et al. Transperineal permanent seed implantation of “low-risk” prostate cancer. Strahlentherapie und Onkologie 2006;182: Battermann J, et al. Results of permanent prostate brachytherapy, 13 years of experience at a single institution. Radiotherapy & Oncology 2004;71:23-28. Livsey J, et al. Hypofractionated conformal radiotherapy in carcinoma of the prostate: five-year outcome analysis. Int J Radiat Oncol Biol Phys 2003;57(5): Lederman G.S, et al. Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy. Int J Radiat Oncol Biol Phys 2001; 49(5): Kuban D, et al. Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70(1): (78Gy) Berglund R, et al. Limited pelvic lymph node dissection at the time of radical prostatectomy does not affect 5-year failure rates for low, intermediate and high risk prostate cancer: results from CaPSURE. J Urology 2007;177: Khaksar S, et al. Interstitial low dose rate brachytherapy for prostate cancer- A focus on intermediate- and high-risk disease. Clinical Oncology 2006;18: Hull G, et al. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urology 2002;167: Sylvester J, et al. Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: The Seattle experience. Int J Radiat Oncol Biol Phys 2003;57(4) Giberti C, et al. Radial retropubic prostatectomy versus brachytherapy for low-risk prostatic cancer: a prospective study. World J Urol 2009;27: (RP) Giberti C, et al. Radial retropubic prostatectomy versus brachytherapy for low-risk prostatic cancer: a prospective study. World J Urol 2009;27: (Seeds) Kupelian P, et al. Hypofractionated intersity-modulated radiotherapy (70 GY at 2.5GY per fraction) for localized prostate cancer: Cleveland clinic experience. Int J Radiat Oncol Biol Phys 2007;68(5): Kupelian P, et al. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: A large scale single institution experience with radical prostatectomy and external-beam radiotherapy. J Clinical Oncology 2002;20(16): (RP) Kupelian P, et al. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: A large scale single institution experience with radical prostatectomy and external-beam radiotherapy. J Clinical Oncology 2002;20(16): (EBRT) Peschel R, et al. Iodine 125 versus palladium 103 implants for prostate cancer: Clinical outcomes and complications. The Cancer Journal 2004;10(3): Crouzet S, et al. Multicentric Oncologic Outcomes of High Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: Misraї V, et al. Oncologic control provided by HIFU therapy as single treatment in men with localized prostate cancer. World J Urol 2008;26: Nobes JP, et al. Biochemical relapse-free survival in 400 patients treated with I-125 prostate brachytherapy: the Guildford experience. Prostate Cancer & Prostatic Disease 2009;12: (Seeds) Nobes JP, et al. Biochemical relapse-free survival in 400 patients treated with I-125 prostate brachytherapy: the Guildford experience. Prostate Cancer & Prostatic Disease 2009;12: (Seeds & ADT) Shapiro E, et al. Long-Term outcomes in younger men following permanent prostate brachytherapy. J Urol 2009;181: (<60 yrs old) Shapiro E, et al. Long-Term outcomes in younger men following permanent prostate brachytherapy. J Urol 2009;181: (>60 yrs old) 96. Crook, J et al. 10-Year Experience with I-125 Prostate Brachytherapy at the Princess Margaret Hospital: Results for 1,100 Patients. Int J Radiat Oncol Bio Phys 2011;80(5): 97. Goldner, G et al. Comparison of seed brachytherapy or external beam radiotherapy (70Gy or 74Gy) in 919 low-risk prostate cancer patients. Stathentherapie und Onkol 2012;4: (Brachy) 98. Goldner, G et al. Comparison of seed brachytherapy or external beam radiotherapy (70Gy or 74Gy) in 919 low-risk prostate cancer patients. Stathentherapie und Onkol 2012;4: (EBRT) 99.Lubbe, W et al. Biochemical and clinical experience with real-time intraoperatively planned permanent prostate brachytherapy. Brachytherapy 2012;11(3): 201. Zamboglou et al ( GermaNy) HDR Interstitial Brachytherapy as monotherapy for Clinically Localized PCa Int J Radiat Oncol Bio Phys 85 (3) p , 2012 202. Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 63 HIFU 34 Protons ← Years from Treatment → Hypo EBRT 91 49 11 HDR Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of 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 97 92 96 113 14 Seeds & ADT 66 25 110 27 + 22 13 8 48 201 4 75 62 37 81 6 44 86 114 35 82 60 EBRT & ADT 69 41 71 33 32 10 65 85 39 Treatment Success 103 98 84 31 72 99 29 101 112 28 67 111 89 42 94 95 61 93 18 88 115 EBRT & Seeds 105 24 38 73 54 102 36 5 16 19 47 78 43 2 26 12 64 55 52 202 40 83 58 1 Robot RP 100 87 106 76 56 7 107 104 77 9 70 80 108 41 15 45 57 74 79 109 59 20 Surgery 53 90 CRYO 1st Group References: Kupelian P, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (RP) Thames H, et al. Increasing external beam dose for T1-T2 prostate cancer: Effect on risk groups. Int J Radiat Oncol Biol Phys 2006;65(4): (Open) Martin AG, Roy J, Beaulieu L, et al. Permanent prostate implant using high activity seeds and inverse planning with fast simulated annealing algorithm: A 12-Year Canadian experience. Int J Radiat Oncol Biol Phys 2007;67(2): Potters L, et al.12-Year outcomes following permanent prostate brachytherapy in patients with clinically localized prostate cancer. J Urology 2005;173: Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Zelefsky M, et al. Five-Year outcome of Intraoperative conformal permanent I-125 interstitial implantation for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 2007;67(1):65-70. Boorjian S, et al. Mayo Clinic validation of the D'Amico risk group classification for predicting survival following radical prostatectomy. J Urology 2008;179: Critz J, et al. 10-Year disease free survival rates after simultaneous irradiation for prostate cancer with a focus on calculation and methodology. J Urology 2004;172: Kuban D, et al. Long-Term multi-institutional analysis of stage T1-T2 prostate cancer treated with radiotherapy in the PSA era. Int J Radiat Oncol Biol Phys 2003;57(4): Weight C, et al. Limited pelvic lymph node dissection does not improve biochemical relapse free survival at 10-years after radical prostatectomy in patients with low risk prostate cancer. J Urology 2008;71(1): Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-Free Survival After Prostate Brachytherapy. J Urol 2005;66(5): Merrick G, et al. Androgen deprivation therapy does not impact cause-specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2006;65(3):669-67 Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Community Oncology 2007;4(4): Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Zelefsky M, et al. Long-term results of conformal radiotherapy for prostate cancer: Impact of dose escalation in biochemical tumor control and distant metastases-free survival outcomes. Int J Radiat Oncol Biol Phys 2008;71(4): Pickles T, et al. Brachytherapy or Conformal External Radiotherapy for Prostate Cancer: A single-Institutional Matched Pair Analysis. Int J Radiat Oncol Biol Phys 2010; 76(1): (EBRT) Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb Morris W, et al. Population-based Study of Biochemical and Survival Outcomes After Permanenet 125I Brachytherapy for Low and Intermediate-risk Prostate Cancer. Urol 2009; 73(4); Bhatta-Dhar N, et al. No difference in 6 year biochemical failure rates with or without pelvic lymph node during radical prostatectomy in low risk patients with prostate cancer. Urology 2004;63(3): Zietman A, et al. Comparison of conventional dose vs high dose conformal radiation therapy in clinically localized Adenocarcinoma of the prostate. JAMA 2005;294(10): & Correction: JAMA 2008; 299(8): Nguyen P, et al. Biochemical recurrence after radical prostatectomy for prevalent versus incident cases of prostate cancer. Cancer 2008;113(11): Taira A, et al. Natural history of clinically staged low- and intermediate risk prostate cancer treated with monotherapeutic permanent interstitial brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): Demanes J, et al. Excellent results from high dose rate brachytherapy and external beam for prostate cancer are not improved by Androgen deprivation. Amer J Clin Oncol 2009;32(4): Stone N, et al. Local control following permanent prostate brachytherapy: Effect of high biologically effective dose on biopsy results and oncologic outcomes. Int J Radiat Oncol Biol Phys 2010;76(2): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Protons) Zeitman A, et al. Randomized trial comparing conventional dose with high dose conformal radiation therapy in early-stage Adenocarcinoma of the prostate: Long term results from proton radiation oncology group/American College of Radiology J Clin Oncol 2010;28(7): Menon M, et al. Biochemical recurrence following robot-assisted radical prostatectomy: Analysis of 1384 patients with a median 5-year follow-up. Eur Urol. 2010;58: Kane CJ, et al. Outcomes after radical prostatectomy among men who are candidates for active surveillance: Results from the SEARCH database urology. Urol 2010;76(3): Ellis R, et al. Ten year outcomes : The clinical utility of single photon emission computed tomography/computed tomography capromab pendetide (prostascint) in a cohort diagnosed with localized prostate cancer. Int J Radiat Oncol Biol Phys 2011; 81(1): Epub date: Hinnen, K. et al. Long term biochemical and survival outcome of 921 patients treated with I-125 permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): Zelefsky et al. Comparison of Tumor Control and toxicity Outcomes of IMRT and Brachytherapy for Patients with Favorable Risk PCa J Urology 2011; 77(4): Epub date: (Seeds) Burri, R. et al. Young Men Have Equivalent Biochemical outcomes Compared With Older Men After Treatment With Brachytherapy For Prostate Cancer. Int J Radiat Oncol Biol Phys 2010; 77(5): Jabbari S, et al. Equivalent biochemical control and improved prostate-specific antigen nadir after permanent prostate seed implant brachytherapy versus high-dose three-dimensional conformal radiotherapy and high-dose conformal proton beam radiotherapy boost. Int J Radiat Oncol Biol Phys 2010;76(1): (Seeds) 100. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (Seeds) 101. Kupelian P, Kuban D, Thames H, et al. Radical prostatectomy, external beam radiotherapy <72 Gy, external beam radiotherapy ≥72 Gy, permanent seed implantation, or combined seeds/external beam radiotherapy for stage T1-T2 prostate cancer. Int J Radiat Oncol Biol Phys 2004;58:(1): (EBRT) 102. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Brachy) 103. Coen, J et al. Comparison of High-Dose-Rate Proton Radiotherapy and Brachytherapy in Localized Prostate Cancer: A Case-Matched Analysis. Int J Radiat Oncol Biol Phys 2012;81(1):e25-e31. (Protons) 105. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 104. Sylvester, J, Grimm P et at Fifteen Year Biochemical RFS CSS, OS Following I-125 Prostate Brachytherapy in Clinically localized prostate cancer Int J Radiat Oncol Biol Phys 2011;81;376-81: 106. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 107. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 108. Mullins, J et al. Radical prostatectomy outcome in men 65 years old or older with low risk prostate cancer. J Urol 2012;187(5): 109. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 110. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 111 Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 112. Ding , F et al Twelve Month PSA values and perineural invasion as strong independent variables of long term biochemical outcome after prostate brachytherapy IJROP 84 (4) p 962-7, 2012 113. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 114. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 115. Mullins et al ( JH) The Impact of RRProstaatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: Blasko J, et al. Palladium-103 brachytherapy for prostate carcinoma. Int J Radiat Oncol Biol Phys 2000;46(4): Demanes D, et al. High-Dose-Rate Intensity-Modulated Brachytherapy with External Beam Radiotherapy for Prostate Cancer: California Endocurietherapy;s 10-Year results. Int J Radiat Oncol Bio Phys 2005;61(5): Grimm P, et al. 10-year biochemical (prostate-specific antigen) control of prostate cancer with I-125 brachytherapy. Int J Radiat Oncol Biol Phys 2001;51(1):31-40. Hernandez D, et al. Contemporary evaluation of the D'Amico risk classification of prostate cancer. J Urol 2007; 70(5): Kupelian P, et al.Improved Biochemical relapse-free survuval with increased external radiation doses in patients with localized prostate cancer: the combined experience of nine institutions in patients treated in 1994 and Int J Radiat Oncol Biol Phys 2005;61(2): Merrick G, et al. Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy. Int J Radiat Oncol Biol Phys 2005;61(1): Vora S, et al. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Bio Phys 2007;68(4): Merrick G, et al. Brachytherapy inmen aged <54 years with clinically localized prostate cancer. BJU Int 2006;98: Bahn D, et al. Targeted cryoablation of the prostate: 7 year outcome in the primary treatment of prostate cancer. Urol 2002;60(Supp 2A):3-11. Phan T, et al. High dose rate brachytherapy as a boost for the treatment of localized prostate cancer. J Urol 2007;177: Cahlon O, et al. Ultra high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Biol Phys 2008;71(2): Sylvester J, et al. 15-Year biochemical relapse free survival in clinical stage T1-T3 prostate cancer following combined external beam radiotherapy and brachytherapy; Seattle experience. Int J Radiat Oncol Biol Phys 2007;67(1):57-64. Higgins G, et al. Outcome analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy. Int J Radiat Oncol Biol Phys 2006;65(4): Kollmeier M, et al. Biochemical outcomes after prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality. Int J Radiat Oncol Biol Phys 2003;57(3): Stone N, et al. Customized dose prescription for permanent prostate brachytherapy: Insights from a multicenter analysis of dosimetry outcomes. Int J Radiat Oncol Biol Phys 2007;69(5): Beyer D, et al. Relative influence of Gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. Ellis R, et al. Biochemical disease-free survival rates following definitive low-dose rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. Kwok Y, et al. Risk group stratification in patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Biol Phys 2002;53(3): Blana A, et al. Eight years’ experience with high-intensity focused ultrasonography for treatment of localized prostate cancer. J Urol 2008;72(6): Lawton, C et al. Long-term Results of a Phase II Trial of Ultrasound-Guided Radioactive Implantation of the Prostate for Definitive Management of Localized Adenocarcinoma of the Prostate (RTOG ) Int J Radiat Oncol Bio Phys 2011;81(1):1-7. Zelefsky M, et al. High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer. J Urol 2001;166: (81Gy) Khuntia D, et al. Recurrence free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate-specific antigen era. Cancer 2004;100(6): Blana A, et al. First Analysis of the Long-Term results with Transrectal HIFU in Patients with Localised prostate Cancer. Eurr Urology 2008;53: Henry A, et al. Outcomes following Iodine-125 monotherapy for localized prostate cancer: the results of Leeds 10-year single-center brachytherapy experience. Int J Radiat Oncol Biol Phys 2010;76(1):50-56. Aizer A, et al. Radical prostatectomy vs. intensity-modulated radiation therapy in the management of localized prostate adenocarcinoma. Radiotherapy and Oncology 2009; 93: Gómez-Iturriaga Piña A, et al. Median 5 year Follow-up of I-125 Brachytherapy as Monotherapy in Men aged <55 Years with Favorable Prostate Cancer. J Urology 2010;75(6): & Gómez-Iturriaga Piña A, et al. Biochemical Disease-free rate toxicicty for Men treated with I-125 prostate Brachytherapy with D90> 180GY. Int J Radia Oncol Bio Phys 2010;78(2): Prada P, et al. Prostate-specific antigen relapse-free survival and side effects in 734 patients with up to 10 years of follow-up with localized prostate cancer treated by permanent Iodine-125 implants. BJU Int 2010;106(1):32-36. Rene N, et al. Hypofractionated radiotherapy for favorable risk prostate cancer. Int J Radiat Oncol Biol Phys 2010;77(3): Lawton C, et al. Results of a Phase II Trial of Transrectal Ultrasound-guided permanent radioactive implantation of the prostate for definitive management of localized adenocarcinoma of the prostate (radiation therapy oncology group 98-05). Int J Radiat Oncol Bio Phys 2007;67(1):39-47. Deger S, et al. High dose rate (HDR) brachytherapy with conformal radiation therapy for localized prostate cancer. Eurr Urology 2005;47(4): Colberg J, et al. Surgery versus implant for early prostate cancer: results from a single institution, Cancer J 2007;13(4): (RP) Colberg J, et al. Surgery versus implant for early prostate cancer: results from a single institution, Cancer J 2007;13(4): (Seeds) D’Amico A, et al. Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 2002;95(2): (RP) D’Amico A, et al. Biochemical outcome after radical prostatectomy or external beam radiation therapy for patients with clinically localized prostate carcinoma in the prostate specific antigen era. Cancer 2002;95(2): (EBRT) Block T, et al. Transperineal permanent seed implantation of “low-risk” prostate cancer. Strahlentherapie und Onkologie 2006;182: Battermann J, et al. Results of permanent prostate brachytherapy, 13 years of experience at a single institution. Radiotherapy & Oncology 2004;71:23-28. Livsey J, et al. Hypofractionated conformal radiotherapy in carcinoma of the prostate: five-year outcome analysis. Int J Radiat Oncol Biol Phys 2003;57(5): Lederman G.S, et al. Retrospective stratification of a consecutive cohort of prostate cancer patients treated with a combined regimen of external-beam radiotherapy and brachytherapy. Int J Radiat Oncol Biol Phys 2001; 49(5): Kuban D, et al. Long-term results of the M.D. Anderson randomized dose-escalation trial for prostate cancer. Int J Radiat Oncol Biol Phys 2008;70(1): (78Gy) Berglund R, et al. Limited pelvic lymph node dissection at the time of radical prostatectomy does not affect 5-year failure rates for low, intermediate and high risk prostate cancer: results from CaPSURE. J Urology 2007;177: Khaksar S, et al. Interstitial low dose rate brachytherapy for prostate cancer- A focus on intermediate- and high-risk disease. Clinical Oncology 2006;18: Hull G, et al. Cancer control with radical prostatectomy alone in 1,000 consecutive patients. J Urology 2002;167: Sylvester J, et al. Ten-year biochemical relapse-free survival after external beam radiation and brachytherapy for localized prostate cancer: The Seattle experience. Int J Radiat Oncol Biol Phys 2003;57(4) Giberti C, et al. Radial retropubic prostatectomy versus brachytherapy for low-risk prostatic cancer: a prospective study. World J Urol 2009;27: (RP) Giberti C, et al. Radial retropubic prostatectomy versus brachytherapy for low-risk prostatic cancer: a prospective study. World J Urol 2009;27: (Seeds) Kupelian P, et al. Hypofractionated intersity-modulated radiotherapy (70 GY at 2.5GY per fraction) for localized prostate cancer: Cleveland clinic experience. Int J Radiat Oncol Biol Phys 2007;68(5): Kupelian P, et al. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: A large scale single institution experience with radical prostatectomy and external-beam radiotherapy. J Clinical Oncology 2002;20(16): (RP) Kupelian P, et al. Comparison of the efficacy of local therapies for localized prostate cancer in the prostate-specific antigen era: A large scale single institution experience with radical prostatectomy and external-beam radiotherapy. J Clinical Oncology 2002;20(16): (EBRT) Peschel R, et al. Iodine 125 versus palladium 103 implants for prostate cancer: Clinical outcomes and complications. The Cancer Journal 2004;10(3): Crouzet S, et al. Multicentric Oncologic Outcomes of High Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: Misraї V, et al. Oncologic control provided by HIFU therapy as single treatment in men with localized prostate cancer. World J Urol 2008;26: Nobes JP, et al. Biochemical relapse-free survival in 400 patients treated with I-125 prostate brachytherapy: the Guildford experience. Prostate Cancer & Prostatic Disease 2009;12: (Seeds) Nobes JP, et al. Biochemical relapse-free survival in 400 patients treated with I-125 prostate brachytherapy: the Guildford experience. Prostate Cancer & Prostatic Disease 2009;12: (Seeds & ADT) Shapiro E, et al. Long-Term outcomes in younger men following permanent prostate brachytherapy. J Urol 2009;181: (<60 yrs old) Shapiro E, et al. Long-Term outcomes in younger men following permanent prostate brachytherapy. J Urol 2009;181: (>60 yrs old) 96. Crook, J et al. 10-Year Experience with I-125 Prostate Brachytherapy at the Princess Margaret Hospital: Results for 1,100 Patients. Int J Radiat Oncol Bio Phys 2011;80(5): 99.Lubbe, W et al. Biochemical and clinical experience with real-time intraoperatively planned permanent prostate brachytherapy. Brachytherapy 2012;11(3): 98. Goldner, G et al. Comparison of seed brachytherapy or external beam radiotherapy (70Gy or 74Gy) in 919 low-risk prostate cancer patients. Stathentherapie und Onkol 2012;4: (EBRT) 97. Goldner, G et al. Comparison of seed brachytherapy or external beam radiotherapy (70Gy or 74Gy) in 919 low-risk prostate cancer patients. Stathentherapie und Onkol 2012;4: (Brachy) 201. Zamboglou et al ( Germany) HDR Interstitial Brachytherapy as monotherapy for Clinically Localized PCa Int J Radiat Oncol Bio Phys 85 (3) p , 2012 202. Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 63 HIFU 34 Protons ← Years from Treatment → Hypo EBRT 91 49 11 HDR Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of 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 Gleason Score 7 or Stage T2b 3/27/2017

22 INTERMEDIATE RISK RESULTS
% PSA Progression Free EBRT + ADT 24 Robot RP 14 23 13 37 49 35 158 151 Seeds + ADT 15 44 153 34 40 + Treatment Success 16 4 38 EBRT & Seeds 30 36 45 152 39 156 6 12 31 42 Hypo EBRT 43 47 27 18 17 Seeds Alone 5 26 28 150 157 9 157 152 7 155 41 29 159 154 1 48 2 10 8 11 46 1st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172: 4 Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(4): 5 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (RP) 6 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 8 Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Bio Phys 2003;57(4): 9 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT) 10 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (RP) 11 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (Seeds) 12 Martin, A et al. Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Bio Phys 2007;67(2): 13 Merrick G, et al. Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J Urology 2005;66(5): 15 Phan, T, et al. High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer. J Urology 2002;177: 16 Burri, R et al. Young Men Have Equivalent Biochmical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer Int J Radiat Oncol Bio Phys 2010; 77(5): 17 Potters, L et al. 12 year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer J Urol 2005;173: 18 Rossi, C et al. Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Comm Oncol 2007;4: 19 (Open) 20 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Low int) 21 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Mid int) 22 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (High int) 23 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds) 24 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds & EBRT) 25 (Open) 26 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT & Seeds) 27. Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: 28 Zelefsky, M et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176: 29 Zelefsky, M et al. Multi Institutional Analysis of Long term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Biol Phys 2007;67(2): 30. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 31. Lawton, C et al. Long-term results of an RTOG phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol Bio Phys 2012;82(5):e795-e801. 32 (Open) (Open) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3): 37. Taira, A et al. Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): 38. Demanes, J et al. Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Amer J Clin Oncology 2009;32(4): 39. Stone, N et al. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int J Radiat Oncol Bio Phys 2010;76(2): Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id ): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58: (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Rad Oncol Biol Phys 2010;76(5): 47. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 48. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 49. Herbert, C et al. Outcomes following inodine-125 brachytherapy in patients with gleason 7, intermediate risk prostate cancer: A population-based cohort study. Radiother Oncol 2012;103(2): 150. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 151.Cury, F et al. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment-risk prostate cancer- long term results. Int J Rad Oncol Biol Phys ;82(4): 152. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost vs EBRT alone for PCa. IROBP 85(3) p 153. Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p 154. Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 155. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 156. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 159. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 20 HDR ← Years from Treatment → 155 EBRT, Seeds + ADT 21 22 Protons Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of Prostate Cancer Center of Seattle

23 INTERMEDIATE RISK RESULTS
Weighted EBRT & Seeds Brachy % PSA Progression Free 24 23 13 Robot RP 14 37 49 35 158 151 34 Seeds + ADT 15 44 153 40 + 16 4 30 36 38 EBRT & Seeds 45 152 39 156 6 12 31 3 42 Hypo EBRT 43 47 17 27 18 Seeds Alone 5 26 28 150 Treatment Success 9 157 152 7 155 41 29 159 154 1 48 2 10 8 11 46 EBRT 1st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172: 4 Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(4): 5 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (RP) 6 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 8 Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Bio Phys 2003;57(4): 9 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT) 10 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (RP) 11 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (Seeds) 12 Martin, A et al. Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Bio Phys 2007;67(2): 13 Merrick G, et al. Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J Urology 2005;66(5): 15 Phan, T, et al. High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer. J Urology 2002;177: 16 Burri, R et al. Young Men Have Equivalent Biochmical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer Int J Radiat Oncol Bio Phys 2010; 77(5): 17 Potters, L et al. 12 year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer J Urol 2005;173: 18 Rossi, C et al. Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Comm Oncol 2007;4: 19. (Open) 20 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Low int) 21 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Mid int) 22 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (High int) 23 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds) 24 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds & EBRT) 25 . (Open) 26 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT & Seeds) 27 . Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: 28 Zelefsky, M et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176: 29 Zelefsky, M et al. Multi Institutional Analysis of Long term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Biol Phys 2007;67(2): 30. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360.) 31. Lawton, C et al. Long-term results of an RTOG phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol Bio Phys 2012;82(5):e795-e801. (Open) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3): 37. Taira, A et al. Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): 38. Demanes, J et al. Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Amer J Clin Oncology 2009;32(4): 39. Stone, N et al. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int J Radiat Oncol Bio Phys 2010;76(2): Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id ): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58: (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Rad Onc Biol Phys 2010;76(5): 47. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 48. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 49. Herbert, C et al. Outcomes following inodine-125 brachytherapy in patients with gleason 7, intermediate risk prostate cancer: A population-based cohort study. Radiother Oncol 2012;103(2): 150. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 151. Cury, F et al. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment-risk prostate cancer- long term results. Int J Rad Oncol Biol Phys ;82(4): 152. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 153. Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p 154. Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 155. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 156. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 157. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 158. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 159. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p Surgery 20 HDR 155 EBRT, Seeds + ADT ← Years from Treatment → 21 22 Protons Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of Prostate Cancer Center of Seattle

24 INTERMEDIATE RISK RESULTS
>40 months follow-up or less than 100 patients % PSA Progression Free EBRT + ADT 54 56 104 59 24 59 66 55 23 13 Robot RP 37 79 14 49 35 59 158 92 98 151 153 34 Seeds + ADT Treatment Success 15 44 96 40 + 109 30 57 16 4 EBRT & Seeds 36 45 68 69 38 58 105 99 77 152 107 12 39 156 31 83 82 97 6 106 42 73 Hypo EBRT 108 51 91 3 64 43 47 72 62 63 93 86 71 17 27 18 50 81 95 Seeds Alone 74 67 90 26 28 150 5 9 52 157 152 78 70 7 155 65 103 102 29 76 41 154 159 60 100 1 48 110 85 88 53 8 87 2 10 75 101 11 46 84 1st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172: 4 Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(4): 5 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (RP) 6 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 8 Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Bio Phys 2003;57(4): 9 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT) 10 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (RP) 11 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (Seeds) 12 Martin, A et al. Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Bio Phys 2007;67(2): 13 Merrick G, et al. Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J Urology 2005;66(5): 15 Phan, T, et al. High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer. J Urology 2002;177: 16 Burri, R et al. Young Men Have Equivalent Biochmical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer Int J Radiat Oncol Bio Phys 2010; 77(5): 17 Potters, L et al. 12 year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer J Urol 2005;173: 18 Rossi, C et al. Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Comm Oncol 2007;4: 19 (Open) 20 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Low int) 21 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Mid int) 22 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (High int) 23 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds) 24 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds & EBRT) 25 . (Open) 26 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT & Seeds) 27 Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: ) 28 Zelefsky, M et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176: 29 Zelefsky, M et al. Multi Institutional Analysis of Long term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Biol Phys 2007;67(2): 30 Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360.) 31. Lawton, C et al. Long-term results of an RTOG phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol Bio Phys 2012;82(5):e795-e801. 32. (Open) (Open) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3): 37. Taira, A et al. Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): 38. Demanes, J et al. Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Amer J Clin Oncology 2009;32(4): 39. Stone, N et al. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int J Radiat Oncol Bio Phys 2010;76(2): Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id ): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58: (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): 47. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 48. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 49. Herbert, C et al. Outcomes following inodine-125 brachytherapy in patients with gleason 7, intermediate risk prostate cancer: A population-based cohort study. Radiother Oncol 2012;103(2): 150. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 151. Cury, F et al. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment-risk prostate cancer- long term results. Int J Rad Oncol Biol Phys ;82(4): 152. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 153. Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p 154. Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 155. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 156. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 157. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 158. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 159. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: 50. Hernandez D, et al. Contemporary Evaluation of the D'Amico Risk Classification of Prostate Cancer. Urology 2007;70(5): 51. Koontz B, et al. Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer. Brachytherapy 2009;8: 52. Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000:47(1): (RP) 53. Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000:47(1): (Seeds) 54. Merrick G, et al. Brachytherapy in Men aged <54 years with clinically localized prostate cancer. BJU Int 2006;98: 55. Merrick G, et al. Impact of Supplemental External beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After permanent Prostate Brachytherapy. Int J Oncol Bio Phys, 2005;61(1): (seeds) 56. Merrick G, et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Oncol Bio Phys, 2005;61(1): (seeds & EBRT) 57. Nobes J, et al. Biochemical Relapse-Free Survival in 400 Patients Treated with I-125 Prostate Brachytherapy: the Guildford Experience. Prostate cancer & Prostatic Disease 2009;12:61-66. 58. Demanes D, et al. High-Dose-Rate Intensity-Modulated Brachytherapy with external beam radiotherapy for prostate cancer: California Endocurietherapy’s 10-Year results. Int J Radiat Oncol Bio Phys 2005;61(5): 59. Yamada Y, et al. Favorable clinical outcomes of three-dimensional computer-optimized high-dose-rate prostate brachytherapy in the management of localized prostate cancer. Brachytherapy 2006;5: 60. Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Comm Oncol 2007;4(4): 61. (Open) 62. Yassa M, et al. Combined hypofractionated radiation and hormone therapy for the treatment of intermediate-risk prostate cancer. Int J Radiat Oncol Bio Phys 2008;71(1):58-63. 63. Cahlon O, et al . Ultra-high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Bio Phys 2008;71(2): 64. Sylvester J, et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy; Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-. 65. Cohen J, et al. Ten-Year Biochemical Disease Control for patients with Prostate Cancer Treated with Cyrosurgery as Primary Therapy. J Urol 2008;71(3): 66. Bachand F, et al. An Eight-Year Experience of HDR Brachytherapy Boost for Localized Prostate cancer: Biopsy and PSA outcome. Int J Radiat Oncol Bio Phys 2009;73(3): 67. Beyer D, et al. Relative influence of Gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. 68. Ellis R, et al. Biochemical Disease-free Survival rates following Definitive Low-Dose-Rate Prostate Brachytherapy with Dose Escalation to Biologic Target Volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. 69. Kuban D, et al. Long term results of the MD Anderson randomized dose escalation trial for prostate cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 70. Blana A, et al. Eight Years’ Experience with High-Intensity Focused Ultrasonography for Treatment of localized prostate cancer. J Urol 2008;72(6): 71. Grimm P, et al. 10-Year Biochemical (Prostate-specific antigen) control of prostate cancer with I-125 Brachytherapy. Int J Radiat Oncol Bio Phys 2001;51(1):31-40. 72. Shapiro E, et al. Long-Term Outcomes in Younger Men Following Permanent Prostate Brachytherapy. J Urology 2009;181: (Seeds <60yr old) 73. Shapiro E, et al. Long-Term Outcomes in Younger Men Following Permanent Prostate Brachytherapy. J Urology 2009;181: (Seeds >60yr old) 74. Zietman A, et al. Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clincially Localized Prostate Cancer. JAMA 2005;294(10): & CORRECTION JAMA 2008;299(8): 75. Kwok Y, et al. Risk Group Stratification in Patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Bio Phys 2002;53(3): 76. Zelefsky M, et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75-81 Gy ) 77. Khunita D, et al. Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate specific antigen era. Cancer 2004;100(6): 78. Vora S, et al. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Bio Phys 2007;68(4): 79. Stone N, et al. Customized Dose prescription for Permanent Prostate Brachytherapy : Insights from Multicenter Analysis of Dosimetry Outcomes. Int J Radiat Oncol Bio Phys 2007;69(5): (High dose: >200Gy) 80. Misrai V, et al. Oncologic Control provided by HIFU therapy as single treament with clinically localized prostate cancer. World J Urol 2008;26: 81. Henry, A, et al. Outcomes Following Iodine-125 Monotherapy for localized Prostate Cancer: The Results of Leeds 10-year single-center brachytherapy experience. Int. J. Radiat Oncol Bio Phys 2010;76(1):50-56. 82. Aizer A, et al. Radical Prostatectomy vs. Intensity-Modulated Radiation Therapy in the Management of Localized Prostate Cancer. Radiotherapy and Oncology 2009;93: 83. Prada P, et al. Prostate-Specific Antigen Relapse-Free Survival and Side-Effects in 734 Patients with up to 10 years of Follow-up with Localized Prostate Cancer Treated by permanent 125-Iodine Implants. BJU Int 2010;106(1):32-36. 84. Vassil A, et al. Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after Radical Prostatectomy, External Beam Radiation Therapy, or Permanent Seed Implantation. Urology 2010;76(5): (Robot) 85. Deger S, et al. High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urol 2005;47: 86. D’Amico A, et al. Biochemical Outcome after Radical Prostatectomy or External Beam Radiation Therapy for Patients with Clinically Localized Prostate Carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (low vol- RP) 87. D’Amico A, et al. Biochemical Outcome after Radical Prostatectomy or External Beam Radiation Therapy for Patients with Clinically Localized Prostate Carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (low vol- EBRT) 88. Battermann J, et al. Results of Permanent Prostate Brachytherapy, 13 years of experience at a Single Institution. Radiotherapy & Oncol 2004;71:23-28. 89. Livsey J, et al. Hypofractionated Conformal Radiotherapy In Carcinoma of the Prostate: five-year outcome analysis. Int J Radiat Oncol Bio Phys 2003;57(5): 90. Lederman G, et al. Retrospective Stratification of a Consecutive Cohort of Prostate Cancer Patients Treated with a Combined Regimen of External-beam Radiotherapy and Brachytherapy. Int J Radiat Oncol Bio Phys 2001;49(5): 91. Kollmeier M, et al. Biochemical Outcomes after Prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality. Int J Radiat Oncol Bio Phys 2003;57(3): 92. Khaksar S, et al. Interstitial Low Dose Rate Brachytherapy for Prostate Cancer- A Focus on Intermediate & High Risk Disease. Clinical Oncol 2006;18: 93. Hull G, et al. Cancer Control with Radical Prostatectomy alone in 1000 Consecutive Patients. J Urol 2002;167: 94. Higgins G, et al. Outcome Analysis of 300 Prostate Cancer Patients Treated With Neoadjuvant Androgen Deprivation & Hypofractionated Radiotherapy. Int J Radiat Oncol Bio Phys 2006;65(4): 95. Sylvester J, et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): 96. Zelefsky M, et al. Five-Year Outcome of Intraoperative Conformal Permanent I-125 Interstitial Implantation for Patients With Clinically Localized Prostate Cancer. Int J Oncol Bio Phys 2007;67(1):65-70. 97. Blasko J, et al. Palladium-103 Brachytherapy for Prostate Carcinoma. Int J Radiat Oncol Biol Phys 2000;46(4): Stock, R, et al. Impact of Hormonal Therapy on Intermediate Risk Prostate Cancer Treated with Combination Brachytherapy and External Beam Irradiation. J Urol 2010;183: 99. Kupelian P, et al. Hypofractionated Intensity-Modulated Radiotherapy (70Gy at 2.5Gy per fraction) for Localized Prostate Cancer: Cleveland Clinic Experience. Int J Radiat Oncol Bio Phys 2007;68(5): 100. Tang J, et al. A prospective dose Escalation Trial of High-dose-rate Brachyhteapy Boost for Prostate Cancer: Evidence of hypofractionation efficacy? Brachytherapy 2006;5: 101. Crouzet S, et al. Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: 102. Colberg J, et al. Surgery versus Implant for early Prostate Cancer: Results from a Single Institution, Cancer 2007;13(4): (RP) 103. Colberg J, et al. Surgery versus Implant for early Prostate Cancer: Results from a Single Institution, Cancer 2007;13(4): (Seeds) 104. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: (HDR) 105. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: (IMRT) 106. Goldner, G et al. Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients. Radiother Oncol 2012;103(2): (EBRT) 107. Goldner, G et al. Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients. Radiother Oncol 2012;103(2): (Seeds) 108. Edelman, S et al. High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity. Int J Radiat Oncol Bio Phys 2012;83(5): (EBRT alone) 109. Edelman, S et al. High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity. Int J Radiat Oncol Bio Phys 2012;83(5): (EBRT & ADT) 110. Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 94 89 20 HDR 155 EBRT, Seeds + ADT ← Years from Treatment → 21 Protons 80 22 Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of 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 56 104 59 24 66 55 14 23 13 Robot RP 37 EBRT 79 49 35 158 92 98 151 34 Seeds + ADT 15 44 96 153 40 + 109 57 16 4 EBRT & Seeds 30 36 45 68 69 38 58 99 77 156 105 82 152 107 12 39 31 83 97 6 106\\\\\\0\\\\\ 42 73 Hypo EBRT 108 51 91 3 64 43 72 62 63 93 47 86 71 17 27 18 50 28 150 81 95 Seeds Alone 74 67 90 26 5 9 52 Treatment Success 152 78 65 157 70 7 155 103 102 41 29 76 154 159 60 100 1 48 110 85 88 53 8 87 2 10 75 101 11 46 84 1st Group References: Bahn, D et al. Targeted Cryo-Ablation of the Prostate:7 yr Outcomes in Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 3 Critz, F et al. 10-Year Disease Free Survival Rates after Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation and Methodology. J Urology 2004;172: 4 Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal high Dose Brachytherapy Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(4): 5 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (RP) 6 Klein E, et al. Outcomes for Intermediate Risk Prostate Cancer: Are There Advantage For Surgery, External Beam, or Brachytherapy. Urologic Oncology 2009;27(1): (Seeds) 7 Kupelian, P et al. Imporved biochemial Relapse-Free Survival With Increased External Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in patients in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 8 Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Bio Phys 2003;57(4): 9 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT) 10 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (RP) 11 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (Seeds) 12 Martin, A et al. Permanent Prostate Implant Using High activity Seeds and Inverse Planning with Fast simulated annealing Algorithm: 12 Year Canadian Experience Int J Radiat Oncol Bio Phys 2007;67(2): 13 Merrick G, et al. Androgen Deprivation Therapy Dose not Impact Cause Specific Overall Survival after Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): 14 Merrick G, et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. J Urology 2005;66(5): 15 Phan, T, et al. High Dose Rate Brachytherapy as a Boost for the Treatment of Localized Prostate Cancer. J Urology 2002;177: 16 Burri, R et al. Young Men Have Equivalent Biochmical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer Int J Radiat Oncol Bio Phys 2010; 77(5): 17 Potters, L et al. 12 year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer J Urol 2005;173: 18 Rossi, C et al. Conformal Proton Beam Radiation Therapy for Prostate Cancer: Concepts & Clinical Results. Comm Oncol 2007;4: 19 (Open) 20 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Low int) 21 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (Mid int) 22 Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups Int J Radiat Oncol Bio Phys 2006;65(4): (High int) 23 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds) 24 Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008; 72(2): (Seeds & EBRT) 25 (Open) 26 Kupelian, P et al. Radical Prostatectomy, External Beam Radiotherapy <72 Gy, External Beam Radiotherapy ≥72 Gy, Permanent Seed Implantation, or Combined Seeds/External Beam Radiotherapy for Stage T1-T2 Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(1): (EBRT & Seeds) 27 Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: 28 Zelefsky, M et al. Long Term Outcome of High Dose Intensity Modulated Radiation Therapy for Patients With Clinically Localized Prostate Cancer. J Urology 2006;176: 29 Zelefsky, M et al. Multi Institutional Analysis of Long term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Biol Phys 2007;67(2): 30 Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 31. Lawton, C et al. Long-term results of an RTOG phase II trial (00-19) of external-beam radiation therapy combined with permanent source brachytherapy for intermediate-risk clinically localized adenocarcinoma of the prostate. Int J Radiat Oncol Bio Phys 2012;82(5):e795-e801. 32. (Open) (Open) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & EBRT) Ho, A et al. Radiation Dose Predicts for Biochemical Control in Intermediate-Risk Prostate Cancer Patients Treated with Low-dose-rate Brachytherapy. Int J Radiat Oncol Biol Phys 2009;75(1): (Seeds & ADT) 36. Galalae, R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer: Is Escalation to Very High Biologically Equivalent Dose Beneficial in All Prognostic Risk Groups? Strahlenther Onkol 2006;182(3): 37. Taira, A et al. Natural History of Clinically Staged Low and Intermediate risk Prostate Cancer Treated with Monotherapeutic Permanent Interstitial Brachytherapy Int J Radiat Oncol Bio Phys 2010;76(2): Update Paper: Taira, A et al. Long-Term Outcomes for Clinically Licalized Prostate Cancer Treated with Permanene Interstitial Brachytherapy. Int J Radiat Oncol Bio Phys, 2011;79(5): 38. Demanes, J et al. Excellent Results from HDR Brachytherapy and EBRT for PCA are not Improved by Androgen deprivation Amer J Clin Oncology 2009;32(4): 39. Stone, N et al. Local Control Following Permanent Prostate Brachytherapy: Effect of High Biologically Effective Dose on Biopsy Results and Oncologic Outcomes Int J Radiat Oncol Bio Phys 2010;76(2): Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Radiation and Brachytherapy J Oncology 2010; 2010(Art. Id ): 6 pages. Menon, M et al. Biochemical Recurrence Following Robot Assisted RP: Analysis of 1384 patients with a median 5 year Follow-up. Eur Urol 2010; 58: (Robot) Munro, N et al. ( Leeds) Outcomes for Gleason Score 7, intermediate risk Localized Prostate Cancer Treated with I-125 monotherapy over 10 years. Radiother Oncol 2010;96(1):34-37. Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (RP) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Proatate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (Seeds) Vassil, A et al. ( Cleveland Clinic) Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after RP, EBRT, or Permanent Seed Implantation Urology 2010;76(5): (EBRT) Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): 47. Gonzales , S et al RP vs EBRT for Localized PCa: Long Term Effect on Biochemical Ocntrol Ann Surg Oncol ; 48. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 49. Herbert, C et al. Outcomes following inodine-125 brachytherapy in patients with gleason 7, intermediate risk prostate cancer: A population-based cohort study. Radiother Oncol 2012;103(2): 150. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 151. Cury, F et al. Single-fraction high-dose-rate brachytherapy and hypofractionated external beam radiation therapy in the treatment-risk prostate cancer- long term results. Int J Rad Oncol Biol Phys ;82(4): 152. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 153. Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p 154. Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 155. Michalski et al. Clinical outcomes of patient treated with 3 D conformal RT (74-79Gy) ( 3D-CRT) for PCa on RTOG 9406 Int J Radiat Oncol Biol Phys 83(3) p 156. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 157. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 158. Morris et al (BCCA) Population Based 10 year Oncologic Outcomes after low dose rate brachytherapy for low risk and intermediate risk PCA Cancer 8 p ,2013 159. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: 50. Hernandez D, et al. Contemporary Evaluation of the D'Amico Risk Classification of Prostate Cancer. Urology 2007;70(5): 51. Koontz B, et al. Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer. Brachytherapy 2009;8: 52. Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000:47(1): (RP) 53. Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000:47(1): (Seeds) 54. Merrick G, et al. Brachytherapy in Men aged <54 years with clinically localized prostate cancer. BJU Int 2006;98: 55. Merrick G, et al. Impact of Supplemental External beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After permanent Prostate Brachytherapy. Int J Oncol Bio Phys, 2005;61(1): (seeds) 56. Merrick G, et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Oncol Bio Phys, 2005;61(1): (seeds & EBRT) 57. Nobes J, et al. Biochemical Relapse-Free Survival in 400 Patients Treated with I-125 Prostate Brachytherapy: the Guildford Experience. Prostate cancer & Prostatic Disease 2009;12:61-66. 58. Demanes D, et al. High-Dose-Rate Intensity-Modulated Brachytherapy with external beam radiotherapy for prostate cancer: California Endocurietherapy’s 10-Year results. Int J Radiat Oncol Bio Phys 2005;61(5): 59. Yamada Y, et al. Favorable clinical outcomes of three-dimensional computer-optimized high-dose-rate prostate brachytherapy in the management of localized prostate cancer. Brachytherapy 2006;5: 60. Rossi C, et al. Conformal proton beam radiation therapy for prostate cancer: concepts and clinical results. Comm Oncol 2007;4(4): 61. (Open) 62. Yassa M, et al. Combined hypofractionated radiation and hormone therapy for the treatment of intermediate-risk prostate cancer. Int J Radiat Oncol Bio Phys 2008;71(1):58-63. 63. Cahlon O, et al . Ultra-high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Bio Phys 2008;71(2): 64. Sylvester J, et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy; Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57- 65. Cohen J, et al. Ten-Year Biochemical Disease Control for patients with Prostate Cancer Treated with Cyrosurgery as Primary Therapy. J Urol 2008;71(3): 66. Bachand F, et al. An Eight-Year Experience of HDR Brachytherapy Boost for Localized Prostate cancer: Biopsy and PSA outcome. Int J Radiat Oncol Bio Phys 2009;73(3): 67. Beyer D, et al. Relative influence of Gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. 68. Ellis R, et al. Biochemical Disease-free Survival rates following Definitive Low-Dose-Rate Prostate Brachytherapy with Dose Escalation to Biologic Target Volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. 69. Kuban D, et al. Long term results of the MD Anderson randomized dose escalation trial for prostate cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 70. Blana A, et al. Eight Years’ Experience with High-Intensity Focused Ultrasonography for Treatment of localized prostate cancer. J Urol 2008;72(6): 71. Grimm P, et al. 10-Year Biochemical (Prostate-specific antigen) control of prostate cancer with I-125 Brachytherapy. Int J Radiat Oncol Bio Phys 2001;51(1):31-40. 72. Shapiro E, et al. Long-Term Outcomes in Younger Men Following Permanent Prostate Brachytherapy. J Urology 2009;181: (Seeds <60yr old) 73. Shapiro E, et al. Long-Term Outcomes in Younger Men Following Permanent Prostate Brachytherapy. J Urology 2009;181: (Seeds >60yr old) 74. Zietman A, et al. Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clincially Localized Prostate Cancer. JAMA 2005;294(10): & CORRECTION JAMA 2008;299(8): 75. Kwok Y, et al. Risk Group Stratification in Patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Bio Phys 2002;53(3): 76. Zelefsky M, et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75-81 Gy ) 77. Khunita D, et al. Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate specific antigen era. Cancer 2004;100(6): 78. Vora S, et al. Analysis of biochemical control and prognostic factors in patients treated with either low-dose three-dimensional conformal radiation therapy or high-dose intensity-modulated radiotherapy for localized prostate cancer. Int J Radiat Oncol Bio Phys 2007;68(4): 79. Stone N, et al. Customized Dose prescription for Permanent Prostate Brachytherapy : Insights from Multicenter Analysis of Dosimetry Outcomes. Int J Radiat Oncol Bio Phys 2007;69(5): (High dose: >200Gy) 80. Misrai V, et al. Oncologic Control provided by HIFU therapy as single treament with clinically localized prostate cancer. World J Urol 2008;26: 81. Henry, A, et al. Outcomes Following Iodine-125 Monotherapy for localized Prostate Cancer: The Results of Leeds 10-year single-center brachytherapy experience. Int. J. Radiat Oncol Bio Phys 2010;76(1):50-56. 82. Aizer A, et al. Radical Prostatectomy vs. Intensity-Modulated Radiation Therapy in the Management of Localized Prostate Cancer. Radiotherapy and Oncology 2009;93: 83. Prada P, et al. Prostate-Specific Antigen Relapse-Free Survival and Side-Effects in 734 Patients with up to 10 years of Follow-up with Localized Prostate Cancer Treated by permanent 125-Iodine Implants. BJU Int 2010;106(1):32-36. 84. Vassil A, et al. Five Year Biochemical recurrence Free Survival for Intermediate Risk Prostate Cancer after Radical Prostatectomy, External Beam Radiation Therapy, or Permanent Seed Implantation. Urology 2010;76(5): (Robot) 85. Deger S, et al. High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urol 2005;47: 86. D’Amico A, et al. Biochemical Outcome after Radical Prostatectomy or External Beam Radiation Therapy for Patients with Clinically Localized Prostate Carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (low vol- RP) 87. D’Amico A, et al. Biochemical Outcome after Radical Prostatectomy or External Beam Radiation Therapy for Patients with Clinically Localized Prostate Carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (low vol- EBRT) 88. Battermann J, et al. Results of Permanent Prostate Brachytherapy, 13 years of experience at a Single Institution. Radiotherapy & Oncol 2004;71:23-28. 89. Livsey J, et al. Hypofractionated Conformal Radiotherapy In Carcinoma of the Prostate: five-year outcome analysis. Int J Radiat Oncol Bio Phys 2003;57(5): 90. Lederman G, et al. Retrospective Stratification of a Consecutive Cohort of Prostate Cancer Patients Treated with a Combined Regimen of External-beam Radiotherapy and Brachytherapy. Int J Radiat Oncol Bio Phys 2001;49(5): 91. Kollmeier M, et al. Biochemical Outcomes after Prostate brachytherapy with 5-year minimal follow-up: importance of patient selection and implant quality. Int J Radiat Oncol Bio Phys 2003;57(3): 92. Khaksar S, et al. Interstitial Low Dose Rate Brachytherapy for Prostate Cancer- A Focus on Intermediate & High Risk Disease. Clinical Oncol 2006;18: 93. Hull G, et al. Cancer Control with Radical Prostatectomy alone in 1000 Consecutive Patients. J Urol 2002;167: 94. Higgins G, et al. Outcome Analysis of 300 Prostate Cancer Patients Treated With Neoadjuvant Androgen Deprivation & Hypofractionated Radiotherapy. Int J Radiat Oncol Bio Phys 2006;65(4): 95. Sylvester J, et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): 96. Zelefsky M, et al. Five-Year Outcome of Intraoperative Conformal Permanent I-125 Interstitial Implantation for Patients With Clinically Localized Prostate Cancer. Int J Oncol Bio Phys 2007;67(1):65-70. 97. Blasko J, et al. Palladium-103 Brachytherapy for Prostate Carcinoma. Int J Radiat Oncol Biol Phys 2000;46(4): Stock, R, et al. Impact of Hormonal Therapy on Intermediate Risk Prostate Cancer Treated with Combination Brachytherapy and External Beam Irradiation. J Urol 2010;183: 99. Kupelian P, et al. Hypofractionated Intensity-Modulated Radiotherapy (70Gy at 2.5Gy per fraction) for Localized Prostate Cancer: Cleveland Clinic Experience. Int J Radiat Oncol Bio Phys 2007;68(5): 100. Tang J, et al. A prospective dose Escalation Trial of High-dose-rate Brachyhteapy Boost for Prostate Cancer: Evidence of hypofractionation efficacy? Brachytherapy 2006;5: 101. Crouzet S, et al. Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: 102. Colberg J, et al. Surgery versus Implant for early Prostate Cancer: Results from a Single Institution, Cancer 2007;13(4): (RP) 103. Colberg J, et al. Surgery versus Implant for early Prostate Cancer: Results from a Single Institution, Cancer 2007;13(4): (Seeds) 104. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: (HDR) 105. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: (IMRT) 106. Goldner, G et al. Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients. Radiother Oncol 2012;103(2): (EBRT) 107. Goldner, G et al. Comparison between external beam radiotherapy (70Gy/74Gy) and permanent interstitial brachytherapy in 890 intermediate risk prostate cancer patients. Radiother Oncol 2012;103(2): (Seeds) 108. Edelman, S et al. High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity. Int J Radiat Oncol Bio Phys 2012;83(5): (EBRT alone) 109. Edelman, S et al. High-dose radiotherapy with or without androgen deprivation therapy for intermediate-risk prostate cancer: cancer control and toxicity. Int J Radiat Oncol Bio Phys 2012;83(5): (EBRT & ADT) 110. Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 94 Surgery 89 20 HDR 155 EBRT, Seeds + ADT ← Years from Treatment → 21 80 22 Protons Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of Prostate Cancer Center of Seattle

26 High Risk Patient Definition
Zelefsky definition 2 or more factors Gleason > 7 PSA Clinical Stage T1c- T2b D'Amico Gleason Score 8-10 PSA >20 3/27/2017

27 HIGH RISK RESULTS % PSA Progression Free Treatment Success Protons HDR
Surg & EBRT 20 16 109 Surg & ADT 19 18 4 112 108 EBRT & ADT Treatment Success 17 123 122 EBRT & Seeds 131 40 125 37 124 3 43 47 34 127 Hypo EBRT 125 41 2 104 48 128 28 13 10 114 42 24 1 12 8 25 132 133 101 110 106 113 33 21 111 5 118 129 14 126 120 120 120 121 39 119 115 117 103 11 26 7 6 1st Group References: 1. Bahn, D et al. Targeted Cryoablation of the Prostate:7-year Outcomes in the Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. 2. Burri, R et al. Young Men have Equivalent Biochemical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer. Int J Radiat Oncol Bio Phys 2010;77(5): 3. Ploussard, G et al. Radical Prostatectomy of High-Risk Prostate Cancer Defined by Preoperative criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification. Urol 2011;78(3):607-13 4. Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008;72(2): 5. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 6. Carver, B et al. Long Term Outcome following Radical Prostatectomy in Men with Clinical T3 Prostate Cancer. J Urology 2006;176: 7. Cohen, J et al. Ten-Year Biochemical Disease Control in Patients with Prostate Cancer Treated with Cryosurgery as Primary Therapy. Urology 2008;71(3): 8. Critz, Fet al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172: 9 . (0pen) 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3): 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4): (PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 13. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 14. Stenmark, M et al. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated with Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease. Int J Radiat Oncol Bio Phys 2011;81(4): 15. Loeb, S et al. Intermediate-term potency, continence & survival outcomes of radical prostatectomy for clinically high-risk or locally advanced prostate cancer. Urology 2007;69(6): 16. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): (EBRT, Seeds, ADT) 17. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int j Radiat Oncol Bio Phys 2006;65(3): (EBRT & Seeds) 18. Merrick, G et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. Urology 2005;66(5): 19. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT, Seeds, ADT) 21. Mian, B et al. Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone. J Urology 2002;167: 22. Pellizzon, A et al. The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5: 23. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (EBRT) 24. Potters, L et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J Urology 2005;173: 25. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (RP) 26. Sylvester, J et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): Lau, W et al. Radical Prostatectomy for Pathological Gleason 8 or Greater Prostate Cancer: Influence of Concomitant Pathological Variables. J Urol 2002;167: Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int J Radiat Oncol Bio Phys 2006;65(4): 30. Ward, J et al. Radical Prostatectomy for Clinically Advanced (cT3) Prostate Cancer since the advent of PSA testing: 15 year outcome. BJU Int 2005;95:751-6. 31. Zelefsky, M et al. Multi-Institutional Analysis of Long-Term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Bio Phys 2007;67(2): 32. (Open) 33. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol Bio Phys 2008;71(4): (81 Gy) 34. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol bio Phys 2008;71(4): (86 Gy) 35. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75 Gy) 36. (Open) 37. Dattoli, M et al. Long-term Outcomes After Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients Having Intermediate and High-Risk Features. Cancer 2007;110(3): 38. (Open) 39. Zelefsky, M et al. Long Term Outcome Following Three dimensional Conformal/IMRT for Clinical Stage T3 Prostate Cancer. Eurr Urol 2008;53: 40. Yoshioka, Y et al. Monotherapeutic High-dose-rate Brachytherapy for Prostate Cancer: Five-year Results of an Extreme Hypofractionation Regimen with 54Gy in Nine Fractions. Int J Radiat Oncol Bio Phys 2011;80(2): 41. Galalae R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer. Strahlenther Onkol 2006;182(3): 42. Demanes, DJ et al. Excellent Results from High Dose Rate Brachytherapy and External Beam Radiation Therapy for Prostate Cancer are Not Imroved by Androgen Deprivation. Amer J Clin Oncol 2009;32(4): 43. Stock, R et al. Outcomes for patients with High-Grade Prostate Cancer Treated with a Combination of Brachytherapy, EBRT and Hormone therapy. BJU Int 2009;104: 44. (Open) 45. (Open) 46. Rubio-Briones, J et al. Metastatic Progression, Cancer Specific Mortality and Need for Secondary Treatments in Patients with Clinically High Risk Prostate Cancer Treated Initially with Radical Prostatectomy. Actas Urologicas Esanolas 2010;34(7): 47. Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy. J Oncology 2010;2010(Article Id ):6 pages. 48. Menon, M et al. Biochemical Recurrence Following Robot Assisted Radical Prostatectomy: Analysis of 1384 patients with a median 5 year follow-up. Eurr Urol 2010;58: 49. Pierorazio, P et al. Long Term Survival after Radical Prostatectomy for Men with High Gleason Sum in Pathologic Specimen. Urology 2010;76(3): 101. Deger, S et al. (Germany) High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urology 2005;47: 102. Magheli A et al. (Johns Hopkins) Importance of Tumor Location in Patients with High Preoperative PSA Levels ( greater than 20 ng/ml treated with Radical Prostatectomy. J Urology 2007;178: 103. Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 104. Sylvester, J et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy: Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-64. 105. Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients Treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): 106. Hsu, C et al. Comparing Results After Surgery in Patients with Clinical Unilateral T3a Prostate Cnacer Treated with or without neoadjuvent Androgen-Deprivation Therapy. BJU Int 2006;99: 107. Roehl, K et al. Cancer Progression and Survival Rates Following Anatomical Radical Prostatectomy in 3,478 Consecutive Patients: Long Term Results. J Urology 2004;172: 108. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (No ADT) 109. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (Plus ADT) Kuban, D et al. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease? Int J Radiat Oncol Bio Phys 2011;79(5): Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) Prada, P et al. ( Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer. Radiation Oncol 2012;7,31-39. Thomson, D et al. Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and toxicity ; epub June 20. 114. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 115. Yamamoto, S et al. Long-term oncological outcome and risk stratification in men with high-risk prostate cancer treated with radical prostatectomy. Jpn J Clin Oncol 2012;42(6): 116. Berglund, R et al. Ten-year follow-up of neoadjuvant therapy with Goserelin Acetate and Flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study Urol 2012;79(3): 117. Freedland, S et al. Radical Prostatectomy for clinical stage T3a disease. Cancer 2007;109(7): 118. Dearnaley, D et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet 2007;8: 119. Spahn, M et al. Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European mulit-institutional study of 712 patients. Eur Urol 2010;58,1-7. 120. Savdie et al HDR Brachytherapy compared to open RP for the treatmetn of High Risk PCa 10 year Biochemical freedom from relapse BJU 110 ( suppl 4) p 121. Tendulkar, R et al. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Bio Phys 2012;82(4): 122. Agoston et al Moderate dose escalation with sigle fraction HDR brachytherapy for clinically localized int and hihg risk Pca: 5 yr outome of first 100 consecutively treated patients Brachyhterapy 10 (5) p 37584, 2011 123. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 124. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 125. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 126. Vora et al ( Mayo) v Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 127. Bittner et Long Term Outcomes for VERY HIGH RISK PCa treated primarily with a triple modulated approach to include permanent see interstitial Brachytherapy Brachytherapy 11(4) p , 2012 128. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy +ADT high risk) ) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 129. Kotecha et al ( MSKCC) Clinical Outcomes of HDR Brachytherapy and EBRT in the Management of Clinically Localized PCa Brachytherapy 12 p 130. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 131. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 132. Bolla et al Post operative radiotherapy after RP for High Risk PCa: Long Term results of a randomized controlled trial ( EORTC) Lancet p , 2012 133. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 35 130 Protons 31 30 116 46 27 107 102 15 HDR 105 EBRT Seeds + ADT ← Years from Treatment → 23 29 49 Robot RP Hypo EBRT +ADT Prostate Cancer Results Study Group Numbers within symbols refer to references HDR + ADT 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of Prostate Cancer Center of Seattle

28 HIGH RISK RESULTS EBRT, Seeds & ADT % PSA Progression Free Brachy
Weighted EBRT, Seeds & ADT % PSA Progression Free Brachy Surg & EBRT 20 16 109 19 18 Surg & ADT 4 22 112 108 EBRT & ADT 123 17 122 EBRT & Seeds 40 112 131 125 37 124 3 43 127 47 34 Hypo EBRT 125 41 2 104 48 128 28 13 10 114 42 24 1 12 8 25 132 Treatment Success 133 101 110 106 113 33 21 111 5 118 129 14 126 120 120 121 39 119 115 26 Surgery 117 EBRT 103 11 7 6 1st Group References: 1. Bahn, D et al. Targeted Cryoablation of the Prostate:7-year Outcomes in the Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. 2. Burri, R et al. Young Men have Equivalent Biochemical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer. Int J Radiat Oncol Bio Phys 2010;77(5): 3. Ploussard, G et al. Radical Prostatectomy of High-Risk Prostate Cancer Defined by Preoperative criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification. Urol 2011;78(3):607-13 4. Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008;72(2): 5. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 6. Carver, B et al. Long Term Outcome following Radical Prostatectomy in Men with Clinical T3 Prostate Cancer. J Urology 2006;176: 7. Cohen, J et al. Ten-Year Biochemical Disease Control in Patients with Prostate Cancer Treated with Cryosurgery as Primary Therapy. Urology 2008;71(3): 8. Critz, Fet al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172: 9 . (Open) 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3): 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4): (PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 13. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Stenmark, M et al. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated with Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease. Int J Radiat Oncol Bio Phys 2011;81(4): 15. Loeb, S et al. Intermediate-term potency, continence & survival outcomes of radical prostatectomy for clinically high-risk or locally advanced prostate cancer. Urology 2007;69(6): 16. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): (EBRT, Seeds, ADT) 17. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int j Radiat Oncol Bio Phys 2006;65(3): (EBRT & Seeds) 18. Merrick, G et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. Urology 2005;66(5): 19. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT, Seeds, ADT) 21. Mian, B et al. Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone. J Urology 2002;167: 22. Pellizzon, A et al. The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5: 23. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (EBRT) 24. Potters, L et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J Urology 2005;173: 25. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (RP) 26. Sylvester, J et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): 27. Lau, W et al. Radical Prostatectomy for Pathological Gleason 8 or Greater Prostate Cancer: Influence of Concomitant Pathological Variables. J Urol 2002;167: 28. Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: ) 29. Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int J Radiat Oncol Bio Phys 2006;65(4): 30. Ward, J et al. Radical Prostatectomy for Clinically Advanced (cT3) Prostate Cancer since the advent of PSA testing: 15 year outcome. BJU Int 2005;95:751-6. 31. Zelefsky, M et al. Multi-Institutional Analysis of Long-Term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Bio Phys 2007;67(2): 32. (Open) 33. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol Bio Phys 2008;71(4): (81 Gy) 34. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol bio Phys 2008;71(4): (86 Gy) 35. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75 Gy) 36. (Open) 37. Dattoli, M et al. Long-term Outcomes After Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients Having Intermediate and High-Risk Features. Cancer 2007;110(3): 38. (Open) 39. Zelefsky, M et al. Long Term Outcome Following Three dimensional Conformal/IMRT for Clinical Stage T3 Prostate Cancer. Eurr Urol 2008;53: 40. Yoshioka, Y et al. Monotherapeutic High-dose-rate Brachytherapy for Prostate Cancer: Five-year Results of an Extreme Hypofractionation Regimen with 54Gy in Nine Fractions. Int J Radiat Oncol Bio Phys 2011;80(2): 41. Galalae R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer. Strahlenther Onkol 2006;182(3): 42. Demanes, DJ et al. Excellent Results from High Dose Rate Brachytherapy and External Beam Radiation Therapy for Prostate Cancer are Not Imroved by Androgen Deprivation. Amer J Clin Oncol 2009;32(4): 43. Stock, R et al. Outcomes for patients with High-Grade Prostate Cancer Treated with a Combination of Brachytherapy, EBRT and Hormone therapy. BJU Int 2009;104: 44. (Open) 45. (Open) 46. Rubio-Briones, J et al. Metastatic Progression, Cancer Specific Mortality and Need for Secondary Treatments in Patients with Clinically High Risk Prostate Cancer Treated Initially with Radical Prostatectomy. Actas Urologicas Esanolas 2010;34(7): 47. Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy. J Oncology 2010;2010(Article Id ):6 pages. 48. Menon, M et al. Biochemical Recurrence Following Robot Assisted Radical Prostatectomy: Analysis of 1384 patients with a median 5 year follow-up. Eurr Urol 2010;58: Pierorazio, P et al. Long Term Survival after Radical Prostatectomy for Men with High Gleason Sum in Pathologic Specimen. Urology 2010;76(3): Deger, S et al. (Germany) High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urology 2005;47: Magheli A et al. (Johns Hopkins) Importance of Tumor Location in Patients with High Preoperative PSA Levels ( greater than 20 ng/ml treated with Radical Prostatectomy. J Urology 2007;178: Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): Sylvester, J et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy: Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-64. Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients Treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): Hsu, C et al. Comparing Results After Surgery in Patients with Clinical Unilateral T3a Prostate Cnacer Treated with or without neoadjuvent Androgen-Deprivation Therapy. BJU Int 2006;99: Roehl, K et al. Cancer Progression and Survival Rates Following Anatomical Radical Prostatectomy in 3,478 Consecutive Patients: Long Term Results. J Urology 2004;172: Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (No ADT) Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (Plus ADT) Kuban, D et al. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease? Int J Radiat Oncol Bio Phys 2011;79(5): Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) Prada, P et al. Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience. BJU Int 2012;109(12): (1 high risk criteria & 2> high risk criteria) (Study Update: Prada, P et al. Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer. Radiation Oncol 2012;7,31-39.) Thomson, D et al. Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and toxicity ; epub June 20. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): Yamamoto, S et al. Long-term oncological outcome and risk stratification in men with high-risk prostate cancer treated with radical prostatectomy. Jpn J Clin Oncol 2012;42(6): Berglund, R et al. Ten-year follow-up of neoadjuvant therapy with Goserelin Acetate and Flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study Urol 2012;79(3): 117. Freedland, S et al. Radical Prostatectomy for clinical stage T3a disease. Cancer 2007;109(7): 118. Dearnaley, D et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet 2007;8: 119. Spahn, M et al. Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European mulit-institutional study of 712 patients. Eur Urol 2010;58,1-7. 120. Savdie et al HDR Brachytherapy compared to open RP for the treatmetn of High Risk PCa 10 year Biochemical freedom from relapse BJU 110 ( suppl 4) p 121. Tendulkar, R et al. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Bio Phys 2012;82(4): 122. Agoston et al Moderate dose escalation with single fraction HDR brachytherapy for clinically localized int and high risk PCa: 5 yr outcome of first 100 consecutively treated patients Brachytherapy 10 (5) p 37584, 2011 123. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 124. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 125. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 126. Vora et al (Mayo) Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 127. Bittner et Long Term Outcomes for VERY HIGH RISK PCa treated primarily with a triple modulated approach to include permanent see interstitial brachyhterapy Brachytherapy 11(4) p , 2012 128. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy +ADT high risk) ) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 129. Kotecha et al ( MSKCC) Clinical Outcomes of HDR Brachytherapy and EBRT in the Management of Clinically Localized PCa Brachytherapy 12 p 130. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 131. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 132. Bolla et al Post operative radiotherapy after RP for High Risk PCa: Long Term results of a randomized controlled trial ( EORTC) Lancet p , 2012 133. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 35 130 Protons 31 30 116 46 27 107 HDR 102 15 105 EBRT Seeds + ADT ← Years from Treatment → 23 29 49 Robot RP HDR + ADT Prostate Cancer Results Study Group Numbers within symbols refer to references 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of Prostate Cancer Center of Seattle

29 HIGH RISK RESULTS >40 months follow-up or less than 100 patients
% PSA Progression Free 92 65 Surg & EBRT 20 94 81 16 109 19 18 Surg & ADT 80 4 74 108 EBRT & ADT 78 22 112 Treatment Success 123 17 122 67 55 131 EBRT & Seeds 40 75 112 125 37 72 124 3 85 43 76 47 54 34 60 127 Hypo EBRT 9 91 66 41 2 125 79 68 104 71 48 128 57 28 13 64 59 10 42 24 50 56 1 12 8 53 25 114 61 132 101 90 110 89 133 23 62 106 113 33 21 111 93 5 118 14 126 120 120 70 129 121 119 39 119 97 115 95 117 103 98 83 11 82 26 6 7 96 1st Group References: 1. Bahn, D et al. Targeted Cryoablation of the Prostate:7-year Outcomes in the Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. 2. Burri, R et al. Young Men have Equivalent Biochemical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer. Int J Radiat Oncol Bio Phys 2010;77(5): 3. Ploussard, G et al. Radical Prostatectomy of High-Risk Prostate Cancer Defined by Preoperative criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification. Urol 2011;78(3):607-13 4. Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008;72(2): 5. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 6. Carver, B et al. Long Term Outcome following Radical Prostatectomy in Men with Clinical T3 Prostate Cancer. J Urology 2006;176: 7. Cohen, J et al. Ten-Year Biochemical Disease Control in Patients with Prostate Cancer Treated with Cryosurgery as Primary Therapy. Urology 2008;71(3): 8. Critz, Fet al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172: 9. Galalae, R et al. Long-term Outcome by Risk Factors Using Conformal High-Dose-Rate Brachytherapy (HDR-BT) Boost with or without Neoadjuvant Androgen Suppression for Localized Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;58(4): 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3): 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4): (PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. 13. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. 14. Stenmark, M et al. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated with Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease. Int J Radiat Oncol Bio Phys 2011;81(4): 15. Loeb, S et al. Intermediate-term potency, continence & survival outcomes of radical prostatectomy for clinically high-risk or locally advanced prostate cancer. Urology 2007;69(6): 16. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): (EBRT, Seeds, ADT) 17. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int j Radiat Oncol Bio Phys 2006;65(3): (EBRT & Seeds) 18. Merrick, G et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. Urology 2005;66(5): 19. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT, Seeds, ADT) 21. Mian, B et al. Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone. J Urology 2002;167: 22. Pellizzon, A et al. The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5: 23. Dearnely, D et al Escalated dose vs standard dose confromal radiotherapy in prostate cancer First results from the MRC RT101 randomised trial Lancet Oncolo 2007;8:475-87 24. Potters, L et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J Urology 2005;173: 25. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (RP) 26. Sylvester, J et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): 27. Lau, W et al. Radical Prostatectomy for Pathological Gleason 8 or Greater Prostate Cancer: Influence of Concomitant Pathological Variables. J Urol 2002;167: Open) 28. Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int J Radiat Oncol Bio Phys 2006;65(4): 30. Ward, J et al. Radical Prostatectomy for Clinically Advanced (cT3) Prostate Cancer since the advent of PSA testing: 15 year outcome. BJU Int 2005;95:751-6. 31. Zelefsky, M et al. Multi-Institutional Analysis of Long-Term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Bio Phys 2007;67(2): 32. (Open) 33. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol Bio Phys 2008;71(4): (81 Gy) 34. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol bio Phys 2008;71(4): (86 Gy) 35. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75 Gy) 36. (Open) 37. Dattoli, M et al. Long-term Outcomes After Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients Having Intermediate and High-Risk Features. Cancer 2007;110(3): 38. (Open) 39. Zelefsky, M et al. Long Term Outcome Following Three dimensional Conformal/IMRT for Clinical Stage T3 Prostate Cancer. Eurr Urol 2008;53: 40. Yoshioka, Y et al. Monotherapeutic High-dose-rate Brachytherapy for Prostate Cancer: Five-year Results of an Extreme Hypofractionation Regimen with 54Gy in Nine Fractions. Int J Radiat Oncol Bio Phys 2011;80(2): 41. Galalae R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer. Strahlenther Onkol 2006;182(3): 42. Demanes, DJ et al. Excellent Results from High Dose Rate Brachytherapy and External Beam Radiation Therapy for Prostate Cancer are Not Imroved by Androgen Deprivation. Amer J Clin Oncol 2009;32(4): 43. Stock, R et al. Outcomes for patients with High-Grade Prostate Cancer Treated with a Combination of Brachytherapy, EBRT and Hormone therapy. BJU Int 2009;104: 44. (Open) 45. (Open) 46. Rubio-Briones, J et al. Metastatic Progression, Cancer Specific Mortality and Need for Secondary Treatments in Patients with Clinically High Risk Prostate Cancer Treated Initially with Radical Prostatectomy. Actas Urologicas Esanolas 2010;34(7): 47. Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy. J Oncology 2010;2010(Article Id ):6 pages. 48. Menon, M et al. Biochemical Recurrence Following Robot Assisted Radical Prostatectomy: Analysis of 1384 patients with a median 5 year follow-up. Eurr Urol 2010;58: Pierorazio, P et al. Long Term Survival after Radical Prostatectomy for Men with High Gleason Sum in Pathologic Specimen. Urology 2010;76(3): 101. Deger, S et al. (Germany) High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urology 2005;47: 102. Magheli A et al. (Johns Hopkins) Importance of Tumor Location in Patients with High Preoperative PSA Levels ( greater than 20 ng/ml treated with Radical Prostatectomy. J Urology 2007;178: 103. Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 104. Sylvester, J et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy: Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-64. 105. Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients Treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): 106. Hsu, C et al. Comparing Results After Surgery in Patients with Clinical Unilateral T3a Prostate Cnacer Treated with or without neoadjuvent Androgen-Deprivation Therapy. BJU Int 2006;99: 107. Roehl, K et al. Cancer Progression and Survival Rates Following Anatomical Radical Prostatectomy in 3,478 Consecutive Patients: Long Term Results. J Urology 2004;172: 108. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (No ADT) 109. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (Plus ADT) 110. Kuban, D et al. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease? Int J Radiat Oncol Bio Phys 2011;79(5): 111. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 112. Prada, P et al. Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience. BJU Int 2012;109(12): (1 high risk criteria & 2> high risk criteria) (Study Update: Prada, P et al. Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer. Radiation Oncol 2012;7,31-39.) 113. Thomson, D et al. Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and toxicity ; epub June 20. 114. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 115. Yamamoto, S et al. Long-term oncological outcome and risk stratification in men with high-risk prostate cancer treated with radical prostatectomy. Jpn J Clin Oncol 2012;42(6): 116. Berglund, R et al. Ten-year follow-up of neoadjuvant therapy with Goserelin Acetate and Flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study Urol 2012;79(3): 117. Freedland, S et al. Radical Prostatectomy for clinical stage T3a disease. Cancer 2007;109(7): 118. Dearnaley, D et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet 2007;8: 119. Spahn, M et al. Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European mulit-institutional study of 712 patients. Eur Urol 2010;58,1-7. 120. Savdie et al HDR Brachytherapy compared to open RP for the treatmetn of High Risk PCa 10 year Biochemical freedom from relapse BJU 110 ( suppl 4) p ) 121. Tendulkar, R et al. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Bio Phys 2012;82(4): 122. Agoston et al Moderate dose escalation with single fraction HDR brachytherapy for clinically localized int and high risk PCa: 5 yr outcome of first 100 consecutively treated patients Brachytherapy 10 (5) p 37584, 2011 123. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 124. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 125. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb Bittner et Long Term Outcomes for VERY HIGH RISK PCa treated primarily with a triple modulated approach to include permanent see interstitial brachyhterapy Brachytherapy 11(4) p , 2012 128. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy +ADT high risk) ) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 129. Kotecha et al ( MSKCC) Clinical Outcomes of HDR Brachytherapy and EBRT in the Management of Clinically Localized PCa Brachytherapy 12 p 130. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 131. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 201 132. Bolla et al Post operative radiotherapy after RP for High Risk PCa: Long Term results of a randomized controlled trial ( EORTC) Lancet p , 2012 133. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: 50. Aizer A, et al. Radical Prostatectomy vs Intensity-Modulated Radiation Therapy in the Management of Localized Prostate Adenocarcinoma. Radiotherapy and Oncology 2009;93: 51. Battermann J, et al. Results of permanent prostate brachytherapy, 13 years of experience at a single institution. Radiotherapy & Oncology 2004;71:23-28. 52. Berglund R, et al. Limited Pelvic Lymph Node Dissection at the Time of Radical Prostatectomy Does Not Affect 5-Year Failure Rates for Low, Intermediate and High Risk Prostate Cancer: Results From CaPSURE. J Urology 2007;177: 53. Beyer D, et al. Relative influence of gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. 54. Cahlon O, et al. Ultra high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Bio Phys 2008;71(2): 55. Copp H, et al. Tumor Control Outcomes of Patients Treated With Trimodality Therapy For Locally Advanced Prostate Cancer. Urology 2005;65(6): 56. Crouzet S, et al. Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: 57. Demanes D, et al. High-Dose-Rate Intensity Modulated Brachytherapy With External Beam Radiotherapy for Prostate Cancer: California Endocurietherapy's 10-Year Results. Int J Radiat Oncol Bio Phys 2005;61(5): 58. Donohue J, et al. Poorly Differentiated Prostate Cancer Treated With Radical Prostatectomy: Long-Term Outcome and Incidence of Pathological Downgrading. J Urology 2006;176(3): 59. Ellis R, et al. Biochemical disease free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. 60. Fonteyne, V et al. Clinical results after high-dose intentisy-modulated radiotherapy for high-risk prostate cancer. Adv Urol 2012; Article ID 61. Henry A, et al. Outcomes Following Iodine-125 Monotherapy for localized Prostate Cancer: The results of Leeds 10-year single-center brachytherapy experience. Int J Radiat Oncol Bio Phys 2010;76(1):50-56. 62. Hernandez D, et al. Contemporary Evaluation of the D’Amico risk classification of Prostate Cancer. J Urol 2007;70(5): 63. Hong S, et al. Predictions of Outcomes after Radical Prostatectomy in Patients Diagnosed with Prostate Cancer of Biopsy GS > 8 via Contemporary multi (>12)-core prostate biopsy. BJU Int 2011;108(2): 64. Hull G, et al. Cancer control with radical prostatectomy alone in 1000 consecutive patients. J Urology 2002;167: 65. Khaksar S, et al. Interstitial low dose rate brachytherapy for prostate cancer-a focus on intermediate & high risk disease. Clinical Oncology 2006;18: 66. Khuntia D, et al. Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate specific antigen era. Cancer 2004;100(6): 67. Koontz B, et al. Morbidity and Prostate Specific Antigen Control of External Beam Radiation Therapy plus Low Dose Rate Brachytherapy Boost for Low ,Intermediate and High Risk Prostate Cancer. Brachytherapy 2009;8: 68. Kupelian P, et al. Hypofractionated Intensity-Modulated Radiotherapy (70Gy at 2.5Gy per fraction) for Localized Prostate Cancer: Cleveland Clinic Experience. Int J Radiat Oncol Bio Phys 2007;68(5): 69. Kwok Y, et al. Risk Group stratification in patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Bio Phys 2002;53(3): 70. Lederman G, et al. Retrospective Stratification of a Consecutive Cohort of Prostate Cancer Patients Treated with a Combined Regimen of External-beam Radiotherapy and Brachytherapy. Int J Radiat Oncol Bio Phys 2001;49(5): 71. Lee L, et al. Role of Hormonal therapy in the management of intermediate to high risk prostate cancer treated with permanent radioactive seed implantation. Int J Radiat Oncol Bio Phys 2002;52(2): 72. Liauw S, et al. Dose-escalated radiotherapy for hight-risk prostate cancer: outcomes in modern ear with short termandrogen deprivation therapy. Int J Radiat Oncol Bio Phys 2010;77(1): 73. Livsey J, et al. Hypofractionated Conformal Radiotherapy in Carcinoma of the Prostate: five-Year Outcome Analysis. Int J Radiat Oncol Bio Phys 2003;57(5): 74. Nobes J, et al. Biochemical Relapse-Free Survival in 400 Patients Treated with I-125 Prostate Brachytherapy: the Guildford Experience. Prostate Ca & Prostatic Disease 2009;12:61-66. 75. Phan T, et al. High dose rate brachytherapy as a boost for the treatment of localized prostate cancer. J Urology 2007;177: Prada P, et al. High-dose-rate intensity modulated brachytherapy with external-beam radiotherapy improves local and biochemical control in patients with high risk prostate cancer. Clin Transl Oncol 2008;10: Sathya J, et al. Randomized Trial comparing Iridium implants plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 2005;23(5): Stock, R. et al. Combined Modality Treatment in the Management of High Risk Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;59(5): Stone N, et al. Multicenter Analysis of Effect of High Biologic Effective dose on Biochemical Failure and Survival Outcomes in Patients with Gleason 7-10 Prostate cancer Treated with Permanent Prostate Bracyhhterapy. Int J Radiat Oncol Bio Phys 2009;73(2): Stone N, et al. Customized dose Prescription for Permanent Prostate Brachytherapy: Insights From a Multicenter Analysis of Dosimetry Outcomes. Int J Radiat Oncol Bio Phys 2007;69(5): Yamada Y, et al. Favorable Clinical Outcomes of 3-D Computer Optimized High Dose Rate Prostate Brachytherapy in the management of Localized Prostate cancer. Brachytherapy 2006;5: Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #1) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #2) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #3) Zwahlen D, et al. High Dose Rate Brachytherapy in Combination with Conformal External Beam Radiotherapy in the Treatment of Prostate Cancer. Brachytherapy 2010;9:27-35. D’Amico A, et al. Biochemical outcomes after Radical Prostatectomy or External Beam Radiation Therapy for patients with clinically localized prostate carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (RP) D’Amico A, et al. Biochemical outcomes after Radical Prostatectomy or External Beam Radiation Therapy for patients with clinically localized prostate carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (EBRT) Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation. Int J Radiat Oncol Bio Phys 2000;47(1): (seeds) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #4) Higgins G, et al. Outcome Analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy. IJROBP;65(4): 91. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: Zapatero, A et al. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable in High Risk Disease? Int J Radiat Oncol Bio Phys 2011;81(5): Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p Lilleby et al ( Norway) Implementation of HDR brachyhterapy and androgen deprivation in patients with PCa IJROBP;83(3):33-9, 2012 Hiney et al ( Bulgaria) RP as a first line Treatment in patients with initial PSA >20 ng/ml Int Jsurg Oncol ,p article ID # Roder et al ( Denmark) RP in Clinically Localized Hihg Risk PCA Outcome of 231 consecutive patients Scandanavian J of Urology 47: 19-25, 2013 Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 Johansson Hypofractionated Proton Boost combined with EBRT for Treatment of Localized PCa Prostate Cancer ID # p1-14 , 2012 99. (Open) 100. (Open) 35 130 52 63 84 Protons 31 116 46 73 58 27 30 77 107 86 87 15 HDR 88 102 51 105 EBRT Seeds + ADT ← Years from Treatment → 29 69 49 Robot RP HIFU Prostate Cancer Results Study Group Numbers within symbols refer to references HDR + ADT 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of 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 Surg & EBRT 20 94 81 16 109 Surg & ADT 19 18 80 4 74 108 EBRT & ADT 78 22 112 Treatment Success 123 17 55 122 123 67 131 EBRT & Seeds 40 75 112 72 125 37 124 3 85 54 34 60 43 76 127 47 Hypo EBRT 91 66 41 2 125 79 68 104 48 128 10 57 28 71 13 64 59 114 42 24 50 56 1 12 8 53 25 61 132 90 89 133 EBRT 101 110 62 106 113 129 33 21 111 93 5 118 14 126 120 70 39 119 95 98 115 96 103 83 11 26 82 6 7 1st Group References: 1. Bahn, D et al. Targeted Cryoablation of the Prostate:7-year Outcomes in the Primary Treatment of Prostate Cancer. Urology 2002;60(Supp 2A):3-11. 2. Burri, R et al. Young Men have Equivalent Biochemical Outcomes Compared with Older Men After Treatment with Brachytherapy for Prostate Cancer. Int J Radiat Oncol Bio Phys 2010;77(5): 3. Ploussard, G et al. Radical Prostatectomy of High-Risk Prostate Cancer Defined by Preoperative criteria: Oncologic Follow-up in National Multicenter Study in 813 Patients and Assessment of Easy-to-use Prognostic Substratification. Urol 2011;78(3):607-13 4. Bittner, N et al. Primary Causes of Death After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2008;72(2): 5. Boorjian, S et al. Mayo Clinic Validation of the D'Amico Risk Group Classification for Predicting Survival Following Radical Prostatectomy. J Urology 2008;179: 6. Carver, B et al. Long Term Outcome following Radical Prostatectomy in Men with Clinical T3 Prostate Cancer. J Urology 2006;176: 7. Cohen, J et al. Ten-Year Biochemical Disease Control in Patients with Prostate Cancer Treated with Cryosurgery as Primary Therapy. Urology 2008;71(3): 8. Critz, Fet al. 10-year Disease Survival Rates After Simultaneous Irradiation for Prostate Cancer with a Focus on Calculation Methodology. J Urology 2004;172: 9. (Open) 10. Kollmeier, M et al. Biochemical Outcomes After Prostate Brachytherapy with 5-year Minimal follow-up: Importance of patient Selection and implant Quality. Int J Radiat Oncol Bio Phys 2003;57(3): 11. Kuban, D et al. Long-Term Multi-Institutional Analysis of Stage T1-T2 Prostate Cancer Treated with Radiotherapy in the PSA Era. Int J Radiat Oncol Biol Phys 2003;57(4): (PSA:4-10,GS:2-6,>70 Gy) 12. Kuban, D et al. Long-Term Results of the MD Anderson Randomized Dose-Escalation Trial for Prostate Cancer. Int J Radiat Oncol Bio Phys 2008;70(1):67-74. Sabolch, A et al. Gleason Patter 5 is Greatest Risk Factor for Clinical Failure and Death from Prostate Cancer after Dose-Escalation Radiation Therapy and Hormonal Ablation. Int J Radiat Oncol Bio Phys 2011;81(4):e351-e360. Stenmark, M et al. Continued Benefit to Androgen Deprivation Therapy for Prostate Cancer Patients Treated with Dose-Escalated Radiation Therapy Across Multiple Definitions of High-Risk Disease. Int J Radiat Oncol Bio Phys 2011;81(4): 15. Loeb, S et al. Intermediate-term potency, continence & survival outcomes of radical prostatectomy for clinically high-risk or locally advanced prostate cancer. Urology 2007;69(6): 16. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int J Radiat Oncol Bio Phys 2006;65(3): (EBRT, Seeds, ADT) 17. Merrick, G et al. Androgen deprivation therapy does not impact cause specific overall survival after permanent prostate brachytherapy. Int j Radiat Oncol Bio Phys 2006;65(3): (EBRT & Seeds) 18. Merrick, G et al. Prognostic Significance of Perineural Invasion on Biochemical Progression-free Survival after Prostate Brachytherapy. Urology 2005;66(5): 19. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT & Seeds) 20. Merrick, G et al. Impact of Supplemental External Beam Radiotherapy and/or Androgen Deprivation Therapy on Biochemical Outcome After Permanent Prostate Brachytherapy. Int J Radiat Oncol Bio Phys 2005;61(1): (EBRT, Seeds, ADT) 21. Mian, B et al. Outcome of Patients w/ Gleason score 8 or Higher Prostate Cancer following Radical Prostatectomy alone. J Urology 2002;167: 22. Pellizzon, A et al. The Relationship Between the Biochemical Control Outcomes and the Quality of Planning of HDR as a Boost to External Beam Radiotherapy for locally and locally advanced Prostate Cancer using the RTOG-ASTRO Phoenix definition. Int J Med Sci 2008;5: 23. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (EBRT) 24. Potters, L et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients With Clinically Localized Prostate Cancer. J Urology 2005;173: 25. Stokes, S et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation Int J Radiat Oncol Bio Phys 2000;47(1): (RP) 26. Sylvester, J et al. Ten Year Biochemical Relapse Free Survival After External Beam Radiation and Brachytherapy for Localized Prostate Cancer: The Seattle Experience. Int J Radiat Oncol Bio Phys 2003;57(4): Lau, W et al. Radical Prostatectomy for Pathological Gleason 8 or Greater Prostate Cancer: Influence of Concomitant Pathological Variables. J Urol 2002;167: Stone, N et al. Influence of Pretreatment and Treatment Factors on Intermediate to Long-term Outcome After Prostate Brachytherapy. J Urol 2011;185: Thames, H et al. Increasing External Beam Dose for T1-T2 Prostate Cancer: Effect on Risk Groups. Int J Radiat Oncol Bio Phys 2006;65(4): 30. Ward, J et al. Radical Prostatectomy for Clinically Advanced (cT3) Prostate Cancer since the advent of PSA testing: 15 year outcome. BJU Int 2005;95:751-6. 31. Zelefsky, M et al. Multi-Institutional Analysis of Long-Term Outcome for T1-T2 Prostate Cancer Treated with Permanent Seed Implantation. Int J Radiat Oncol Bio Phys 2007;67(2): 32. (Open) 33. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol Bio Phys 2008;71(4): (81 Gy) 34. Zelefsky, M et al. Long-term Results of Conformal Radiotherapy for prostate Cancer: Impact of Dose Escalation in Biochemical Tumor Control and distant Metastases-free Survival Outcomes. Int j Radiat Oncol bio Phys 2008;71(4): (86 Gy) 35. Zelefsky, M et al. High Dose Radiation Delivered by Intensity Modulated Conformal Radiotherapy Improves the Outcome of Localized Prostate Cancer. J Urology 2001;166: (75 Gy) 36. (Open) 37. Dattoli, M et al. Long-term Outcomes After Treatment with Brachytherapy and Supplemental Conformal Radiation for Prostate Cancer Patients Having Intermediate and High-Risk Features. Cancer 2007;110(3): 38. (Open) 39. Zelefsky, M et al. Long Term Outcome Following Three dimensional Conformal/IMRT for Clinical Stage T3 Prostate Cancer. Eurr Urol 2008;53: 40. Yoshioka, Y et al. Monotherapeutic High-dose-rate Brachytherapy for Prostate Cancer: Five-year Results of an Extreme Hypofractionation Regimen with 54Gy in Nine Fractions. Int J Radiat Oncol Bio Phys 2011;80(2): 41. Galalae R et al. Hypofractionated Conformal HDR Brachytherapy in Hormone Naïve Men with Localized Prostate Cancer. Strahlenther Onkol 2006;182(3): 42. Demanes, DJ et al. Excellent Results from High Dose Rate Brachytherapy and External Beam Radiation Therapy for Prostate Cancer are Not Imroved by Androgen Deprivation. Amer J Clin Oncol 2009;32(4): 43. Stock, R et al. Outcomes for patients with High-Grade Prostate Cancer Treated with a Combination of Brachytherapy, EBRT and Hormone therapy. BJU Int 2009;104: 44. (Open) 45. (Open) 46. Rubio-Briones, J et al. Metastatic Progression, Cancer Specific Mortality and Need for Secondary Treatments in Patients with Clinically High Risk Prostate Cancer Treated Initially with Radical Prostatectomy. Actas Urologicas Esanolas 2010;34(7): 47. Dattoli, M et al. Long Term Outcomes for Patients with Prostate Cancer Having Intermediate and High Risk Disease, Treated with Combination External Beam Irradiation and Brachytherapy. J Oncology 2010;2010(Article Id ):6 pages. 48. Menon, M et al. Biochemical Recurrence Following Robot Assisted Radical Prostatectomy: Analysis of 1384 patients with a median 5 year follow-up. Eurr Urol 2010;58: Pierorazio, P et al. Long Term Survival after Radical Prostatectomy for Men with High Gleason Sum in Pathologic Specimen. Urology 2010;76(3): 101. Deger, S et al. (Germany) High Dose Rate (HDR) Brachytherapy with Conformal Radiation Therapy for Localized Prostate Cancer. Eurr Urology 2005;47: 102. Magheli A et al. (Johns Hopkins) Importance of Tumor Location in Patients with High Preoperative PSA Levels ( greater than 20 ng/ml treated with Radical Prostatectomy. J Urology 2007;178: 103. Kupelian P, et al. Improved Biochemical Relapse-Free Survival With Increased Radiation Doses in Patients With Localized Prostate Cancer: The Combined Experience of Nine Institutions in 1994 and Int J Radiat Oncol Bio Phys 2005;61(2): 104. Sylvester, J et al. 15-Year Biochemical Relapse Free Survival in Clinical Stage T1-T3 Prostate Cancer Following Combined External Beam Radiotherapy and Brachytherapy: Seattle Experience. Int J Radiat Oncol Bio Phys 2007;67(1):57-64. 105. Hinnen, K et al. (Netherlands) Long Term Biochemical and Survival Outcome of 921 Patients Treated with I-125 Permanent Prostate Brachytherapy. Int J Radiat Oncol Biol Phys 2010;76(5): 106. Hsu, C et al. Comparing Results After Surgery in Patients with Clinical Unilateral T3a Prostate Cnacer Treated with or without neoadjuvent Androgen-Deprivation Therapy. BJU Int 2006;99: 107. Roehl, K et al. Cancer Progression and Survival Rates Following Anatomical Radical Prostatectomy in 3,478 Consecutive Patients: Long Term Results. J Urology 2004;172: 108. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (No ADT) 109. Merrick, G et al. Prostate Cancer Death is Unlikely in High Risk Patients Following Quality Permanent Seed Implantation. BJU Int 2010;107: (Plus ADT) 110. Kuban, D et al. Long-Term Failure Patterns and Survival in a Randomized Dose-Escalation Trial for Prostate Cancer. Who Dies of Disease? Int J Radiat Oncol Bio Phys 2011;79(5): 111. Busch, J et al. Long-term oncological and continence outcomes after laparoscopic radical prostatectomy: a single-centre experience. BJU Int 2012; 110(11):E (Robot) 112. Prada, P et al. Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience. BJU Int 2012;109(12): (1 high risk criteria & 2> high risk criteria) (Study Update: Prada, P et al. Long-term biochemical results after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy for high risk prostate cancer. Radiation Oncol 2012;7,31-39. 113. Thomson, D et al. Dose-escalated hypofractionated intensity-modulated radiotherapy in high-risk carcinoma of the prostate: outcome and toxicity ; epub June 20. 114. Sooriakumaran, P et al. Biochemical recurrence after robot-assisted radical prostatectomy in a European single-centre cohort with a minimum follow-up time of 5 years. Eur Urol 2012;62(5): 115. Yamamoto, S et al. Long-term oncological outcome and risk stratification in men with high-risk prostate cancer treated with radical prostatectomy. Jpn J Clin Oncol 2012;42(6): 116. Berglund, R et al. Ten-year follow-up of neoadjuvant therapy with Goserelin Acetate and Flutamide before radical prostatectomy for clinical T3 and T4 prostate cancer: update on Southwest Oncology Group Study Urol 2012;79(3): 117. Freedland, S et al. Radical Prostatectomy for clinical stage T3a disease. Cancer 2007;109(7): 118. Dearnaley, D et al. Escalated-dose versus standard-dose conformal radiotherapy in prostate cancer: first results from the MRC RT01 randomised controlled trial. Lancet 2007;8: 119. Spahn, M et al. Outcome predictors of radical prostatectomy in patients with prostate-specific antigen greater than 20 ng/ml: a European mulit-institutional study of 712 patients. Eur Urol 2010;58,1-7. 120. Savdie et al HDR Brachytherapy compared to open RP for the treatmetn of High Risk PCa 10 year Biochemical freedom from relapse BJU 110 ( suppl 4) p 121. Tendulkar, R et al. Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Int J Radiat Oncol Bio Phys 2012;82(4): 122. Agoston et al Moderate dose escalation with single fraction HDR brachytherapy for clinically localized int and high risk PCa: 5 yr outcome of first 100 consecutively treated patients Brachytherapy 10 (5) p 37584, 2011 123. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 124. Arcangeli et al Updated results and patterns of failure in a randomized hypofractionated trial for high risk PCa IJROBP 84 (5) p 125. Khor et al Direct 2 arm comparison shows benefit of HDR brachytherapy boost s EBRT alone for PCa. IROBP 85(3) p 126. Vora et al Nine year outcomes and toxicity in patients treated with IMRT for Localized PCa J Urol Feb 127. Bittner et Long Term Outcomes for VERY HIGH RISK PCa treated primarily with a triple modulated approach to include permanent see interstitial brachyhterapy Brachytherapy 11(4) p , 2012 128. Spratt et al. (MSKCC) Long term outcome of high dose intensity modulated radiation therapy (86 Gy +ADT high risk) ) for patients with clinically localized prostate cancer. Int J Radiat Oncol Biol Phys 85 (3) :686-92,2013 129. Kotecha et al ( MSKCC) Clinical Outcomes of HDR Brachytherapy and EBRT in the Management of Clinically Localized PCa Brachytherapy 12 p 130. Critz et al. 25 year Disease Free Survival Rates after irradiation of PCa calculated with the PSA definition of recurrences used for RP J Urol 189 (3) p , 2013 131. Vargas et al Long Term Outcome and prognostic Factors in patients treated with intraoperatively planned prostate brachytherapy Brachytherapy 12(2) p , 2013 132. Bolla et al Post operative radiotherapy after RP for High Risk PCa: Long Term results of a randomized controlled trial ( EORTC) Lancet p , 2012 133. Mullins et al ( JH) The Impact of RRProstatectomy on cancer Control: the 30 year anniversary J Urol p 2nd Group References: 50. Aizer A, et al. Radical Prostatectomy vs Intensity-Modulated Radiation Therapy in the Management of Localized Prostate Adenocarcinoma. Radiotherapy and Oncology 2009;93: 51. Battermann J, et al. Results of permanent prostate brachytherapy, 13 years of experience at a single institution. Radiotherapy & Oncology 2004;71:23-28. 52. Berglund R, et al. Limited Pelvic Lymph Node Dissection at the Time of Radical Prostatectomy Does Not Affect 5-Year Failure Rates for Low, Intermediate and High Risk Prostate Cancer: Results From CaPSURE. J Urology 2007;177: 53. Beyer D, et al. Relative influence of gleason score and pretreatment PSA in predicting survival following brachytherapy for prostate cancer. Brachytherapy 2003;2:77-84. 54. Cahlon O, et al. Ultra high dose (86.4Gy) IMRT for localized prostate cancer: toxicity and biochemical outcomes. Int J Radiat Oncol Bio Phys 2008;71(2): 55. Copp H, et al. Tumor Control Outcomes of Patients Treated With Trimodality Therapy For Locally Advanced Prostate Cancer. Urology 2005;65(6): 56. Crouzet S, et al. Multicentric Oncologic Outcomes of High-Intensity Focused Ultrasound for Localized Prostate Cancer in 803 patients. Eurr Urol 2010;58: 57. Demanes D, et al. High-Dose-Rate Intensity Modulated Brachytherapy With External Beam Radiotherapy for Prostate Cancer: California Endocurietherapy's 10-Year Results. Int J Radiat Oncol Bio Phys 2005;61(5): 58. Donohue J, et al. Poorly Differentiated Prostate Cancer Treated With Radical Prostatectomy: Long-Term Outcome and Incidence of Pathological Downgrading. J Urology 2006;176(3): 59. Ellis R, et al. Biochemical disease free survival rates following definitive low-dose-rate prostate brachytherapy with dose escalation to biologic target volumes identified with SPECT/CT capromab pendetide. Brachytherapy 2007;6:16-25. 60. Fonteyne, V et al. Clinical results after high-dose intentisy-modulated radiotherapy for high-risk prostate cancer. Adv Urol 2012; Article ID 61. Henry A, et al. Outcomes Following Iodine-125 Monotherapy for localized Prostate Cancer: The results of Leeds 10-year single-center brachytherapy experience. Int J Radiat Oncol Bio Phys 2010;76(1):50-56. 62. Hernandez D, et al. Contemporary Evaluation of the D’Amico risk classification of Prostate Cancer. J Urol 2007;70(5): 63. Hong S, et al. Predictions of Outcomes after Radical Prostatectomy in Patients Diagnosed with Prostate Cancer of Biopsy GS > 8 via Contemporary multi (>12)-core prostate biopsy. BJU Int 2011;108(2): 64. Hull G, et al. Cancer control with radical prostatectomy alone in 1000 consecutive patients. J Urology 2002;167: 65. Khaksar S, et al. Interstitial low dose rate brachytherapy for prostate cancer-a focus on intermediate & high risk disease. Clinical Oncology 2006;18: 66. Khuntia D, et al. Recurrence-free survival rates after external-beam radiotherapy for patients with clinical T1-T3 prostate carcinoma in prostate specific antigen era. Cancer 2004;100(6): 67. Koontz B, et al. Morbidity and Prostate Specific Antigen Control of External Beam Radiation Therapy plus Low Dose Rate Brachytherapy Boost for Low ,Intermediate and High Risk Prostate Cancer. Brachytherapy 2009;8: 68. Kupelian P, et al. Hypofractionated Intensity-Modulated Radiotherapy (70Gy at 2.5Gy per fraction) for Localized Prostate Cancer: Cleveland Clinic Experience. Int J Radiat Oncol Bio Phys 2007;68(5): 69. Kwok Y, et al. Risk Group stratification in patients undergoing permanent I-125 prostate brachytherapy as monotherapy. Int J Radiat Oncol Bio Phys 2002;53(3): 70. Lederman G, et al. Retrospective Stratification of a Consecutive Cohort of Prostate Cancer Patients Treated with a Combined Regimen of External-beam Radiotherapy and Brachytherapy. Int J Radiat Oncol Bio Phys 2001;49(5): 71. Lee L, et al. Role of Hormonal therapy in the management of intermediate to high risk prostate cancer treated with permanent radioactive seed implantation. Int J Radiat Oncol Bio Phys 2002;52(2): 72. Liauw S, et al. Dose-escalated radiotherapy for hight-risk prostate cancer: outcomes in modern ear with short termandrogen deprivation therapy. Int J Radiat Oncol Bio Phys 2010;77(1): 73. Livsey J, et al. Hypofractionated Conformal Radiotherapy in Carcinoma of the Prostate: five-Year Outcome Analysis. Int J Radiat Oncol Bio Phys 2003;57(5): 74. Nobes J, et al. Biochemical Relapse-Free Survival in 400 Patients Treated with I-125 Prostate Brachytherapy: the Guildford Experience. Prostate Ca & Prostatic Disease 2009;12:61-66. 75. Phan T, et al. High dose rate brachytherapy as a boost for the treatment of localized prostate cancer. J Urology 2007;177: Prada P, et al. High-dose-rate intensity modulated brachytherapy with external-beam radiotherapy improves local and biochemical control in patients with high risk prostate cancer. Clin Transl Oncol 2008;10: Sathya J, et al. Randomized Trial comparing Iridium implants plus external-beam radiation therapy with external-beam radiation therapy alone in node-negative locally advanced cancer of the prostate. J Clin Oncol 2005;23(5): Stock, R. et al. Combined Modality Treatment in the Management of High Risk Prostate Cancer. Int J Radiat Oncol Bio Phys 2004;59(5): Stone N, et al. Multicenter Analysis of Effect of High Biologic Effective dose on Biochemical Failure and Survival Outcomes in Patients with Gleason 7-10 Prostate cancer Treated with Permanent Prostate Bracyhhterapy. Int J Radiat Oncol Bio Phys 2009;73(2): Stone N, et al. Customized dose Prescription for Permanent Prostate Brachytherapy: Insights From a Multicenter Analysis of Dosimetry Outcomes. Int J Radiat Oncol Bio Phys 2007;69(5): Yamada Y, et al. Favorable Clinical Outcomes of 3-D Computer Optimized High Dose Rate Prostate Brachytherapy in the management of Localized Prostate cancer. Brachytherapy 2006;5: Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #1) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #2) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #3) Zwahlen D, et al. High Dose Rate Brachytherapy in Combination with Conformal External Beam Radiotherapy in the Treatment of Prostate Cancer. Brachytherapy 2010;9:27-35. D’Amico A, et al. Biochemical outcomes after Radical Prostatectomy or External Beam Radiation Therapy for patients with clinically localized prostate carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (RP) D’Amico A, et al. Biochemical outcomes after Radical Prostatectomy or External Beam Radiation Therapy for patients with clinically localized prostate carcinoma in the Prostate Specific Antigen Era. Cancer 2002;95(2): (EBRT) Stokes S, et al. Comparison of biochemical disease-free survival of patients with localized carcinoma of the prostate undergoing radical prostatectomy, transperineal ultrasound-guided radioactive seed implantation, or definitive external beam irradiation. Int J Radiat Oncol Bio Phys 2000;47(1): (seeds) Yossepowitch O, et al. Radical Prostatectomy for Clinically Localized High Risk Prostate Cancer: Critical Analysis of Risk Assessment Methods. J Urology 2007;178: (Def. #4) Higgins G, et al. Outcome Analysis of 300 prostate cancer patients treated with neoadjuvant androgen deprivation and hypofractionated radiotherapy. IJROBP;65(4): 91. Deutsch, I et al. Comparison of PSA relapse-free survival in patients treated with ultra-high-dose IMRT versus combination HDR brachytherapy and IMRT. Brachytherapy 2010;9: 92. Zapatero, A et al. Long-Term Results After High-Dose Radiotherapy and Adjuvant Hormones in Prostate Cancer: How Curable in High Risk Disease? Int J Radiat Oncol Bio Phys 2011;81(5): 93. Kotecha et al Clinical outcomes of HDR brachytherapy and EBRT in the management of localized PCa Brachytherapy 12 (1) p 94. Lilleby et al ( Norway) Implementation of HDR brachytherapy and androgen deprivation in patients with PCa IJROBP;83(3):33-9, 2012 95. Hiney et al ( Bulgaria) RP as a first line Treatment in patients with initial PSA >20 ng/ml Int Jsurg Oncol ,p article ID # 96. Roder et al ( Denmark) RP in Clinically Localized High Risk PCA Outcome of 231 consecutive patients Scandanavian J of Urology 47: 19-25, 2013 97. Pfeiffer et al. Single Application of HIFU as First Line Therapy for Clinically Localized PCa BJU Int 110 p , 2012 98. Johansson Hypofractionated Proton Boost combined with EBRT for Treatment of Localized PCa Prostate Cancer ID # p1-14 , 2012 99. (Open) 100. (Open) 35 130 52 63 84 Protons 31 30 116 46 73 58 27 77 107 HDR 86 87 15 88 102 51 105 EBRT Seeds + ADT Surgery ← Years from Treatment → 23 29 69 49 Robot RP HIFU Prostate Cancer Results Study Group Numbers within symbols refer to references HDR + ADT 3/27/2017 BJU Int, 2012, Vol. 109(Supp 1) Update of 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 3/27/2017 3/27/2017 31 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 3/27/2017

33 Slide Symbols & Abbreviations (cont.)
= “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 + 3/27/2017

34 Risk Group Definitions
Low Risk Stage: T1 or T2a,b Gleason Score < PSA < 10 ng/ml Intermediate Risk Stage T1 or T Stage T1-2 Gleason Score 7 or Gleason Score 6 PSA < 10 ng/ml PSA ng/ml High Risk Stage T2c or T3 Gleason Score ≥ 8 PSA > 20 ng/mL 3/27/2017

35 For More Information Peter Grimm, DO Lisa Grimm, Research Coordinator
Lisa Grimm, Research Coordinator Or contact a PCRSG member Prostate Cancer Center of Seattle (website & ) 3/27/2017


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