Treatment of Prostate Cancer With Intermittent Versus Continuous Androgen Deprivation: A Systematic Review of Randomized Trials

Abstract

Uncertainty exists regarding benefits of intermittent androgen deprivation (IAD) compared with continuous androgen deprivation (CAD) for treatment of prostate cancer. On the basis of a systematic review of evidence, our aim was to formulate a recommendation for either IAD or CAD to treat relapsing, locally advanced, or metastatic prostate cancer. We searched literature published up to September 2012 from MEDLINE, EMBASE, the Cochrane Library, and major conference proceedings. We included randomized controlled trials comparing IAD and CAD if they reported overall survival (OS) or biochemical/radiologic time to disease progression. Nine studies with 5,508 patients met our criteria. There were no significant differences in time-to-event outcomes between the groups in any studies. The pooled hazard ratio (HR) for OS was 1.02 (95% CI, 0.94 to 1.11) for IAD compared with CAD, and the HR for progression-free survival was 0.96 (95% CI, 0.76 to 1.20). More prostate cancer-related deaths with IAD tended to be balanced by more deaths not related to prostate cancer with CAD. Superiority of IAD for sexual function, physical activity, and general well-being was observed in some trials. Median cost savings with IAD was estimated to be 48%. There is fair evidence to recommend use of IAD instead of CAD for the treatment of men with relapsing, locally advanced, or metastatic prostate cancer who achieve a good initial response to androgen deprivation. This recommendation is based on evidence against superiority of either strategy for time-to-event outcomes and substantial decrease with IAD in exposure to androgen deprivation, resulting in less cost, inconvenience, and potential toxicity.