Hormonal therapy for localized prostate cancer in Japan. The - PowerPoint PPT Presentation

Hormonal therapy for localized prostate cancer in Japan. The outcome of J-CaP database. Shiro Hinotsu 1,12 , Hideyuki Akaza 2,12 , Osamu Ogawa 3,12 , Mototsugu Oya 4,12 , Tadaichi Kitamura 5,12 , Kazuhiro Suzuki 6,12 , Taiji Tsukamoto 7,12 , Seiji Naito 8,12 , Mikio Namiki 9,12 , Kazuo Nishimura 10,12 , Yoshihiko Hirao 11,1 1: Department of Pharmacoepidemiology, Kyoto University, Kyoto, Japan 2: Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan 3: Department of Urology, Kyoto University, Kyoto, Japan 4: Department of Urology, Keio University School of Medicine, Tokyo, Japan 5: Asoka Hospital, Tokyo, Japan 6: Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan 7: Department of Urology, Sapporo Medical University, Sapporo, Japan 8: Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan 9: Department of Urology, Kanazawa University School of Medicine, Kanazawa, Japan 10:Department of Urology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan 11: Department of Urology, Nara Medical University, Kashihara, Japan 12: J-CaP Study Group, Tokyo, Japan

Background • The J-CaP database was established in 2001 when the Japan Study Group of Prostate Cancer (J-CaP Study Group) started a study to gather information on hormone therapy administered to Japanese patients and to analyze the outcomes of treatment. A prostate cancer registry managed by the Japanese Urological Association revealed that 45% of patients diagnosed with localized prostate cancer in 2000 in Japan were treated with hormonal therapy. The J-CaP database is the largest cohort of over 20,000 prostate cancer patients treated with hormonal therapy.

Objectives • To estimate overall survival and cause-specific survival of Japanese patients with localized (or locally advanced) prostate cancer treated with hormonal therapy, using information in the J-CaP database. • To compare overall survival as a primary endpoint of randomized clinical trials performed in Western countries with the outcome of patients in the J-CaP database selected using the inclusion criteria in the randomized trials.

Methods • Overall survival and cause-specific survival of patients in the J-CaP database were estimated by the Kaplan-Meier method. • Overall survival of patients in the J-CaP database was compared with the outcomes of five randomized clinical trials identified from a PubMed search, based on selection of J-CaP patients using the same inclusion and exclusion criteria as those in the protocol of the trials.

Results • 19,275 patients were treated by hormonal therapy in J-CaP database. • 9,127 patients were stratified by D’Amico risk classification into low risk (1,728, 19%), intermediate risk (1,981, 22%) and high risk (5,418, 59%) cases.

Overall survival of J-CaP database stratified by D’Amico risk classification 1 0.8 0.6 Low risk(N=1728) 0.4 Intermediate risk(N=1981) 0.2 High risk(N=5418) 0 0 2 4 6 8 10 Years rs after PADT

Cause specific survival of J-CaP database stratified by D’Amico risk classification 1 0.8 Low risk(N=1728) 0.6 Intermediate risk(N=1981) 0.4 Low risk(N=5418) 0.2 0 0 2 4 6 8 10 Years rs after PADT

Ref. No. No. Intervention Inclusion criteria endpoint Results in RCT Results Number of of (95%CI) from Pts. in J-CaP Pts. J-CaP database database 1) 603 Radiation + CAB T3,T4 N0,Nx M0 7yr or OS 74(70-78) 74.7 2778 T2 PSA>40 or CSS 90(86-93) 89.0 2778 T2 PSA>20 Gleason>=8 Age <80 2) 987 Radiation + Short ADT T1b,c T2a,b N0Nx 10yrOS 62 74.6 6211 M0 Low 67 75.1 1613 PSA <20 Inter 61 71.1 1812 High 53 75.8 1852 3) 349 Radical Prostatectomy T1,2 N0M0 8yrOS 82.1(77.6-85.7) 77.7 7687 PSA <50 Age<65 87.9(81.5-92.2) 91.7 384 Age=>65 77.4(70.5-82.4) 76.8 7303 4) 102 Radiation + ADT T1,2 N0M0 8yr OS 74(64-82) 75.1 5520 PSA 10 to 40 or Gleason 7 to 10 5) 87 Radical Prostatectomy T1,2 N0M0 3yr DFS 33.3(28-84) 72.0 673 Gleason 8-10 PSA <=10 56.2 79.2 170 PSA>10 19.2 69.5 503 Ref.: Reference, Pts.: Patients, CAB: Combined Androgen Blockade, ADT: Androgen Deprivation Therapy, OS: Overall survival, CSS: Cause-specific survival, DFS: Disease free survival, RCT: Randomized clinical trial, CI: Confidence interval

Discussion • The prostate cancer registry 6) managed by the Japanese Urological Association revealed that 45% of patients diagnosed with localized prostate cancer in 2000 in Japan were treated with hormonal therapy. • In an observational study in Japan 7) , the overall survival of patients treated with hormonal therapy (CAB) was similar to the expected survival from vital statistics in Japan. • It is difficult to make a direct comparison of the survival of patients with localized prostate cancer treated with hormonal therapy in Japan with that of patients treated by radical prostatectomy or radiation therapy in Western countries. • The generalizability of results from RCTs should be considered. Comparison of survival data from RCTs with results from an outcome study should be interpreted carefully. • In general, outcomes from RCTs were better than those from outcome studies. • In the present study, the estimated survival in the present outcome study in Japan was not inferior to the results of RCTs in Western countries

Conclusion • Following selection of patients in the J-CaP database based on similar criteria to those used in RCTs of radical treatment in Western countries, Japanese patients with localized (or locally advanced) prostate cancer who were treated with hormonal therapy had similar outcomes to those in the RCTs.

References 1) Warde P, Mason M, Ding K, et al. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 ;378(9809):2104-11. 2) Jones CU, Hunt D, McGowan DG, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011; 365(2):107-18. 3) Bill-Axelson A, Holmberg L, Filén F, et al. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst. 2008; 100(16):1144-54. 4)D'Amico AV, Chen MH, Renshaw AA, et al. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008; 299(3):289-95. 5)Tefilli MV, Gheiler EL, Tiguert R, et al. Role of radical prostatectomy in patients with prostate cancer of high Gleason score. Prostate. 1999; 39(1):60-6. 6)Cancer Registration Committee of the Japanese Urological Association. Clinicopathological statistics on registered prostate cancer patients in Japan: 2000 report from the Japanese Urological Association. Int J Urol. 2005; 12:46-61. 7)Akaza H, Homma Y, Usami M, et al. Efficacy of primary hormone therapy for localized or locally advanced prostate cancer: results of a 10-year follow-up. BJU Int. 2006; 98(3):573-9.