title: Treatment of mCRPC in the AR-axis-targeted therapy-resistant state.
abstract: BACKGROUND
  The increased use of the androgen receptor axis-targeted (ARAT) agents abiraterone and enzalutamide in first- and second-line treatment of metastatic castration-resistant prostate cancer (mCRPC) has improved patient outcomes, but resistance to these agents is inevitable. Early identification of patients with primary or secondary resistance to ARAT therapy is of increasing clinical concern.
  
  
  METHODS
  PubMed and conference proceedings were searched for studies of agents used after progression on abiraterone or enzalutamide. The key search terms (or aliases) used a combination of mCRPC and abiraterone or enzalutamide, and results were limited to clinical trials and comparative or validation studies.
  
  
  CONCLUSIONS
  This systematic review assembles current evidence and provides an approach to treatment using available clinical factors. Issues of patient selection, use of laboratory and clinical biomarkers to identify patients at risk of poor outcomes, and the timing and sequencing of available treatment options are addressed. Our findings reveal a lack of high-level evidence regarding predictive factors and treatment of patients with resistance to ARAT therapy, and a need for further research in this area. In the meantime, we suggest practical strategies to guide management of ARAT treatment-resistant patients based on available data.
authors.affiliation: Division of Medical Oncology, British Columbia Cancer Agency, Vancouver.
authors.forename: K
authors.initials: K
authors.lastname: Chi
authors.affiliation: Department of Oncology, Juravinski Cancer Center, Hamilton.
authors.forename: S J
authors.initials: SJ
authors.lastname: Hotte
authors.affiliation: Department of Medical Oncology, Princess Margaret Cancer Centre, Toronto.
authors.forename: A M
authors.initials: AM
authors.lastname: Joshua
authors.affiliation: Department of Oncology, Cross Cancer Institute, Edmonton.
authors.forename: S
authors.initials: S
authors.lastname: North
authors.affiliation: Department of Urologic Sciences, Vancouver Prostate Centre, Vancouver.
authors.forename: A W
authors.initials: AW
authors.lastname: Wyatt
authors.affiliation: Kaleidoscope Strategic, Toronto.
authors.forename: L L
authors.initials: LL
authors.lastname: Collins
authors.affiliation: Division of Urology, University of Montreal Hospital Center, Montreal, Canada fred.saad@umontreal.ca.
authors.forename: F
authors.initials: F
authors.lastname: Saad
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D011944:Receptors, Androgen / Q000737:chemistry*
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D011944:Receptors, Androgen
keywords: abiraterone; castration-resistant; enzalutamide; prostate cancer; taxanes; treatment sequencing