Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: A systematic review

Objectives. Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been th e subject of 20 randomized trials. The findings range from no expected incr ease in survival in 17 studies to an estimated 3.7 to 7 months' survival im provement noted in 3 studies. Most recently, a 1999 evidence report from th e Agency for Healthcare Research and Quality and a 2000 overview from the P rostate Cancer Trialists Collaborative Group indicated that combined androg en blockade was associated with an approximately 3% to 5% increase in 5-yea r survival. We report herein a systematic review on combined androgen block ade performed by the Cochrane Collaborative Review Group on Prostate Diseas es. Methods. Controlled trials that included a randomization of immediate nonst eroidal antiandrogens with castration versus castration alone for metastati c prostate cancer and provided information on survival were reviewed. infor mation on overall survival, toxicity, progression-free survival, cancer-spe cific survival, and type of nonsteroidal antiandrogen and castration therap ies was abstracted by two independent reviewers. Results. Twenty trials (n = 6320 patients) were included. The pooled odds r atio (OR) for overall survival with combined androgen blockade was 1.03 (95 % confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95 % CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-fr ee survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 227 8 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1. 58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall s urvival progressively increased but was not significant at any follow-up in terval. Conclusions. We find that there is a 5% improvement in the percentage of me n surviving at 5 years (30% vs. 25%) with combined androgen blockade with n onsteroidal antiandrogens as well as improvements in progression-free survi val at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expend itures. UROLOGY 57: 727-732, 2001. (C) 2001, Elsevier Science Inc.