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Table 1.  

Notable Randomized Trials of Combined Androgen Deprivation and External Beam Radiation Therapy in Locally Advanced Prostate Cancer

Androgen Deprivation Therapy: Progress in Understanding Mechanisms of Resistance and Optimizing Androgen Depletion

Authors: William P. Harris, MD ; Elahe A. Mostaghel, MD, PhD ; Peter S. Nelson, MD ; Bruce Montgomery, MDFaculty and Disclosures


Summary and Introduction


Androgen deprivation therapy remains a critical component of treatment for men with advanced prostate cancer, and data support its use in metastatic disease and in conjunction with surgery or radiation in specific settings. Alternatives to standard androgen deprivation therapy, such as intermittent androgen suppression and estrogen therapy, hold the potential to improve toxicity profiles while maintaining clinical benefit. Current androgen deprivation strategies seem to incompletely suppress androgen levels and androgen-receptor-mediated effects at the tissue level. Advances in the understanding of mechanisms that contribute to castration-resistant prostate cancer are leading to rationally designed therapies targeting androgen metabolism and the androgen receptor. The results of large trials investigating the optimization of primary androgen deprivation therapy, including evaluation of intermittent androgen suppression and phase III studies of novel androgen synthesis inhibitors, such as abiraterone acetate, are eagerly awaited.


Prostate cancer is the most common solid tumor and the second most common cause of cancer death among men in the United States,[1] and its worldwide incidence is the second highest of all male non-skin malignancies.[2] At present, approximately 85% of newly diagnosed prostate cancers are localized to the prostate, with the remainder representing invasive or metastatic disease.[3] Recognized treatment options for early-stage disease include surgery, radiation therapy and active surveillance. For many men with metastatic or high-risk localized disease, androgen deprivation is a critical component of therapy, either alone or in combination with other modalities. This Review will provide an overview of historical and contemporary approaches to androgen deprivation in patients with advanced prostate cancer, and address its current clinical indications: either as monotherapy or in combination with local therapy. Mechanisms of resistance to classical androgen deprivation, which might be exploited to therapeutic effect in early and late-stage cancer, will be discussed, as will several promising new therapies that are undergoing early assessment.

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