Yoshiyuki Nagumo1, Mizuki Onozawa2, Takahiro Kojima1, Naoki Terada3, Masaki Shiota4, Koji Mitsuzuka5, Hiroaki Yasumoto6, Hiroaki Matsumoto7, Hideki Enokida8, Takayuki Sugiyama9, Kentaro Kuroiwa10, Toshihiro Saito11, Akira Yokomizo12, Naoki Kohei13, Ken-Ichi Tabata14, Atsushi Takahashi15, Mikio Sugimoto16, Hiroshi Kitamura17, Toshiyuki Kamoto3, Hiroyuki Nishiyama1. 1. Department of Urology, University of Tsukuba, Tsukuba, Ibaraki, Japan. 2. Department of Urology, International University of Health and Welfare, Narita City, Chiba, Japan. 3. Department of Urology, Miyazaki University, Miyazaki, Japan. 4. Department of Urology, Kyushu University, Fukuoka, Japan. 5. Department of Urology, Tohoku University, Sendai, Japan. 6. Department of Urology, Shimane University, Izumo, Japan. 7. Department of Urology, Yamaguchi University, Ube, Japan. 8. Department of Urology, Kagoshima University, Kagoshima, Japan. 9. Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan. 10. Department of Urology, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan. 11. Department of Urology, Niigata Cancer Center Hospital, Niigata, Japan. 12. Department of Urology, Harasanshin Hospital, Fukuoka, Japan. 13. Department of Urology, Shizuoka General Hospital, Shizuoka, Japan. 14. Department of Urology, Kitasato University, Sagamihara, Japan. 15. Department of Urology, Hakodate Goryoukaku Hospital, Hakodate, Japan. 16. Department of Urology, Kagawa University, Kagawa, Japan. 17. Department of Urology, Faculty of Medicine, University of Toyama, Toyama, Japan.
Abstract
OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.
OBJECTIVE: To determine the effect of combined androgen blockade with a first-generation anti-androgen on the prognoses of metastatic hormone-sensitive prostate cancer patients stratified by tumor burden. METHODS: We retrospectively analyzed the cases of metastatic hormone-sensitive prostate cancer patients who were treated with androgen deprivation therapy in 2008-2017 at 30 institutions in Japan. To compare the overall survival and progression-free survival rates of the patients treated with castration monotherapy and combined androgen blockade, we carried out a Cox proportional hazards regression analysis using both inverse probability of treatment weighting and instrumental variables methods. High-burden disease was defined as the presence of four or more bone metastases and/or visceral metastasis. RESULTS: Of 2048 patients, 702 (34.3%) and 1346 (65.7%) patients were classified as the low- and high-burden groups, respectively. In each group, >80% of the patients were treated with combined androgen blockade. Although there was no significant between-group difference in the overall survival according to the androgen deprivation therapy method, in the high-burden group the progression-free survival of the combined androgen blockade-treated patients was significantly better than that of patients treated with castration monotherapy: inverse probability of treatment weighting method, hazard ratio 0.49, 95% confidence interval 0.34-0.71; instrumental variables method, hazard ratio 0.80, 95% confidence interval 0.60-0.98. CONCLUSION: In the high-burden group, combined androgen blockade with a first-generation anti-androgen resulted in superior progression-free survival compared with castration monotherapy. For well-selected metastatic hormone-sensitive prostate cancer patients, the use of combined androgen blockade might still have some suitable scenarios.