Over the past 7 decades androgen-deprivation therapy (ADT) has been the cornerstone of treatment for metastatic non-castrate prostate cancer (NCPC); however, the mechanisms to achieve this goal have evolved over time to include not only bilateral orchiectomy and estrogens, but also gonadotropin-releasing hormone (GnRH) agonists, antagonists, and the inclusion of androgen receptor (AR) blockade. Despite treatment with ADT, most men will progress to castrate-resistant prostate cancer (CRPC). Over the last decade many new treatment options for CRPC have emerged. These new treatments also could have a meaningful role earlier in NCPC. In this review, we outline the biologic drivers of NCPC, review current standard therapy available for NCPC, and discuss the evolving role of new therapeutics in metastatic disease.
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