Intermittent androgen deprivation is a rational standard-of-care treatment for all stages of progressive prostate cancer: results from a systematic review and meta-analysis

The optimal hormone treatment strategy in prostate cancer is uncertain, particularly in patients with metastatic disease. We aimed to compare the relative benefits and harms of intermittent androgen deprivation (IAD) to continuous androgen deprivation (CAD) in all stages of prostate cancer. We included eight randomised control trials (4668 patients) in our systematic review and meta-analysis. Median follow-up ranged from 29 to 118 months. Pooled hazard ratios (HRs) were calculated for overall survival (OS), cancer-specific survival, time to cancer progression and mortality unrelated to prostate cancer. The relative effect of treatment in patients with metastatic and those with non-metastatic disease was compared using pre-planned subgroup analysis. There was no difference in OS between patients treated with IAD and CAD (HR 1.01, 95% confidence interval (CI) 0.93-1.10); nor was there any difference in cancer-specific survival (HR 1.03; 95% CI 0.88-1.21). There was a non-significant trend towards longer time to prostate cancer progression for IAD (HR 0.93, 95% CI 0.84-1.04), raising the possibility of slower selection for castrate resistance. There was no significant difference in OS when analysis was restricted to patients with metastatic disease (HR 1.04, 95% CI 0.91-1.19) or patients without metastatic disease (HR 1.06, 95% CI 0.91-1.23) (test for subgroup differences P=0.84). Most studies found an improvement in quality of life or toxicity profile with IAD. IAD is non-inferior to CAD in terms of OS and cancer-specific survival, and is at least non-inferior in terms of time to progression. This meta-analysis confirms IAD as a valid standard of care for managing prostate cancer patients.