Context: Androgen-deprivation therapy (ADT) plays a pivotal role in the management of locally advanced and metastatic prostate cancer (PCa). When and for how long to apply ADT have remained controversial issues. Objective: To review randomised studies of ADT (orchiectomy or luteinising hormone-releasing hormone analogues) in PCa-both immediate and deferred/adjuvant studies-to elucidate a possible interaction between local treatment and ADT. Evidence acquisition: Published randomised studies on ADT in various stages of PCa were included in this review. Evidence synthesis: Studies of immediate versus deferred ADT without local treatment consistently showed only limited benefit for overall survival (OS; hazard ratio [HR]: 0.90; 95% confidence interval [CI], 0.83-0.97) and cancer-specific survival (CSS; HR: 0.79; 95% CI, 0.71-0.89). In contrast, ADT as an adjuvant to radiation therapy in patients with high-risk localised disease or locally advanced disease was associated with substantial OS and CSS benefits. A similar benefit was seen in patients with proven systemic disease (node-positive patients after radical prostatectomy). Overall, the data suggest a clinically important survival benefit (HR for OS: 0.69; 95% CI, 0.61-0.79) when a local treatment has been applied to the primary tumour. Possible mechanisms of this therapeutic effect are discussed. Conclusions: We conclude that an interaction between local treatment and ADT is suggested by this systematic review. In patients with advanced and aggressive disease who are at a high risk to die from PCa and who are treated for their primary tumour with curative intent, immediate and sustained ADT improves OS and CSS significantly. The local therapy in T3 and/or lymph node-positive disease is an essential part of the optimal treatment. However, this intensive treatment is unnecessary in a substantial number of patients with T3 and/or N1 disease with a slow natural history or high competing death risk. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.