title: Castration-resistant prostate cancer: from new pathophysiology to new treatment.
abstract: BACKGROUND
  Until recently, the only approved agent for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5 years, significant advances in the field have led to the approval of five new agents, each with different mechanisms of action and demonstrating improved overall survival in separate randomized phase 3 trials. Many of these novel agents are now also being evaluated in earlier stages of the disease, which may ultimately lead to even better outcomes.
  
  
  OBJECTIVE
  To summarize the current literature on the management of mCRPC with a particular focus on novel chemotherapy approaches, hormonal approaches, immunotherapy, and radiopharmaceuticals showing survival benefits in phase 3 clinical trials. Emerging therapies in late stages of development are also discussed briefly.
  
  
  METHODS
  A comprehensive search of PubMed, identified studies pertaining to novel therapies evaluated in mCRPC since the initial approval of docetaxel in 2004. Abstracts from major international meetings were hand searched to identify studies of novel agents in late stage development in mCRPC. The Clinical Trials.gov database was used to find ongoing clinical trials in the area of mCRPC. A detailed search of each new agent was also performed to ensure that additional trials of these agents in other stages of the disease were included where relevant.
  
  
  RESULTS
  The main agents discussed are the androgen synthesis inhibitor abiraterone acetate, the androgen receptor inhibitor enzalutamide, the novel taxane chemotherapy cabazitaxel, the immunotherapy sipuleucel-T, and the radiopharmaceutical radium 223. Other emerging agents and a brief discussion of negative phase 3 results are also included.
  
  
  CONCLUSIONS
  It is a very exciting time in the field of mCRPC, where therapeutic advances have improved outcomes in this disease, although once metastatic overall median survival remains a dismal 2-3 years. The key now will be to understand how best to use these new agents, understand the mechanisms of resistance to them, continue to develop novel treatment strategies, and ultimately test these agents earlier in the disease when cure may be possible.
authors: Princess Margaret Hospital, Toronto, ON, Canada. Electronic address: srikala.sridhar@uhn.ca.
authors: Srikala S
authors: SS
authors: Sridhar
authors: Durham VA Medical Center and Duke University Medical Center, Durham, NC, USA.
authors: Stephen J
authors: SJ
authors: Freedland
authors: BC Cancer Agency, Vancouver, BC, Canada.
authors: Martin E
authors: ME
authors: Gleave
authors: Seattle Cancer Centre Alliance, Seattle, WA, USA.
authors: Celestia
authors: C
authors: Higano
authors: Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors: Peter
authors: P
authors: Mulders
authors: Royal Marsden NHS Foundation Trust, Sutton, UK.
authors: Chris
authors: C
authors: Parker
authors: Tulane Cancer Center, New Orleans, LA, USA.
authors: Oliver
authors: O
authors: Sartor
authors: University of Montreal Hospital Center, Montreal, PQ, Canada.
authors: Fred
authors: F
authors: Saad
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D064129:Prostatic Neoplasms, Castration-Resistant / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019275:Radiopharmaceuticals
keywords: Abiraterone; CRPC; Cabazitaxel; Enzalutamide; Novel treatments; Radium-223; Sipuleucel T