Approaches to minimize castration in the treatment of advanced prostate cancer

Kreshnik Zejnullahu, Maria G. Arevalo, Charles J. Ryan, Rahul Aggarwal

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Background Androgen deprivation therapy (ADT) remains the cornerstone of primary systemic treatment for men with metastatic disease and is a commonly applied therapy in the biochemically relapsed setting. Despite the high response rate with ADT, resistance is universal. Furthermore, over the past decade, there has been a growing appreciation for the significant short-term and long-term toxicities of continuous ADT (CADT). The rationale to develop alternative androgen receptor (AR) targeting strategies that seek to minimize or eliminate the need for upfront castration therapy is 2-fold—(1) delay the emergence of AR-independent disease, potentially improving long-term disease outcomes and (2) mitigate the short-term and long-term side effects of CADT, improving quality of life and potentially lessening comorbidities related to ADT including osteoporosis, diabetes, and potentially cardiovascular disease. The 2 most rigorously studied alternatives to CADT include intermittent ADT and peripheral androgen blockade with the use of first-generation or second-generation AR antagonists. Both intermittent ADT and peripheral androgen blockade have been evaluated in the biochemically relapsed and metastatic setting in multiple phase 2 and 3 studies. Aim In the current review, we aim to discuss the data from these studies, as well as the emerging noncastrating strategies.

Original languageEnglish (US)
Pages (from-to)368-374
Number of pages7
JournalUrologic Oncology: Seminars and Original Investigations
Issue number8
StatePublished - Aug 1 2016


  • Androgen deprivation therapy
  • Biochemically recurrent prostate cancer
  • Peripheral androgen blockade

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