CLINICIAN’S CORNERCLINICAL REVIEW Androgen Deprivation Therapy for Prostate Cancer

ANDROGEN DEPRIVATIONthe r apy (ADT; he r e indefined as medical or surgi-cal castration) is the corner-stone treatment of advanced prostate cancer. In 1941, Huggins and Hodges1 first noted the beneficial effects of cas-tration and injection of estrogens in patients with metastatic prostate can-cer. The biological basis of the effect of ADT, the almost ubiquitous ex-pression of the androgen receptor in prostate cancer, and growth depen-dence on the androgen receptor later became clear. Today, in addition to its well-established role in treating patientswith metastatic disease, ADT is sometimes used to treat patients with increasing prostate-specific antigen (PSA) levels after local treatment, even without radiographic or other evidence of metastatic disease. Androgen depriva-tion therapy is also used as adjunct therapy for men undergoing radiation therapy for high-risk localized disease (TABLE 1). Despite frequently dra-matic and sustained responses of many patients to ADT, treatment exposes pa-tients to a host of important adverse ef-fects (TABLE 2). We sought to system-atically review existing evidence regarding the benefits and risks of ADT in contemporary management of local and metastatic prostate cancer. EVIDENCE ACQUISITION We performed MEDLINE searches of the English-language literature (1966 toMarch 2005) using the terms andro-gen deprivation therapy, hormone treat-ment, and prostate cancer. Relevant bib-liographies of literature weremanually reviewed for additional material. In evaluating the benefits of ADT, phase 3 randomized trial data were empha-sized. On review of clinical trials, clini-cal end points of focus, in decreasing order of importance, were survival ben-efit, radiographic progression-free sur-vival, and rising PSA level. Further in-formation was obtained in oral an