title: Approaches to minimize castration in the treatment of advanced prostate cancer.
abstract: 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.
  
  
  
  In the current review, we aim to discuss the data from these studies, as well as the emerging noncastrating strategies.
authors.affiliation: Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.
authors.forename: Kreshnik
authors.initials: K
authors.lastname: Zejnullahu
authors.affiliation: Servicio de Oncologia Medica, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Arevalo
authors.affiliation: Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.affiliation: Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA. Electronic address: Rahul.Aggarwal@ucsf.edu.
authors.forename: Rahul
authors.initials: R
authors.lastname: Aggarwal
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D000728:Androgens; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011788:Quality of Life
chemical_list: D000726:Androgen Antagonists; D000728:Androgens
keywords: Androgen deprivation therapy; Biochemically recurrent prostate cancer; Peripheral androgen blockade