cal castration) is the cornerstone treatment of advanced prostate cancer. In 1941, Huggins and Hodges 1 first noted the beneficial effects of castration and injection of estrogens in patients with metastatic prostate cancer. The biological basis of the effect of ADT, the almost ubiquitous expression of the androgen receptor in prostate cancer, and growth dependence on the androgen receptor later became clear.Today, in addition to its wellestablished role in treating patients with 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 deprivation therapy is also used as adjunct therapy for men undergoing radiation therapy for high-risk localized disease (TABLE 1). Despite frequently dramatic and sustained responses of many patients to ADT, treatment exposes patients to a host of important adverse effects (TABLE 2). We sought to systematically review existing evidence regarding the benefits and risks of ADT in contemporary management of local and metastatic prostate cancer.
EVIDENCE ACQUISITIONWe performed MEDLINE searches of the English-language literature (1966 to March 2005) using the terms androgen deprivation therapy, hormone treatment, and prostate cancer. Relevant bibliographies of literature were manually reviewed for additional material. In evaluating the benefits of ADT, phase 3 randomized trial data were emphasized. On review of clinical trials, clinical end points of focus, in decreasing order of importance, were survival benefit, radiographic progression-free survival, and rising PSA level. Further information was obtained in oral and abstract form at the 2005 Prostate Cancer Symposium meeting, Orlando, Fla, and the 2005 American Society of Clini-cal Oncology meeting, Orlando, Fla. Published guidelines from the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology were also reviewed.