title: Prostate specific antigen only androgen independent prostate cancer: natural history, challenges in management and clinical trial design.
abstract: OBJECTIVE
  There is no current standard of care for patients with nonmetastatic androgen independent prostate cancer, a condition defined by increasing serum prostate specific antigen despite anorchid testosterone levels and no radiographic evidence of metastases. A consensus panel was convened to review data and propose a strategy for trial design and prioritization.
  
  
  METHODS
  Published literature on the natural history of nonmetastatic androgen independent prostate cancer was reviewed. A panel discussion was held, focusing on reviewing current and past trials, and the development of research priorities for patients in this disease state.
  
  
  RESULTS
  Based on 1 report the natural history of nonmetastatic androgen independent prostate cancer is relatively long but heterogeneous. External validation of these published findings has not been performed. Clinical trial design in this setting is impeded by heterogeneity and lack of knowledge about the natural history, prolonged time to clinical end points, such as the development of metastases or death, and a lack of knowledge about how intermediate end points, eg the development of bone metastases, are related to the long-term outcome, eg survival. In clinical practice a reluctance to use therapies with substantial toxicity as well as a lack of outcome data on such patients leaves a vacuum in which there is no standard of care, although secondary hormonal manipulations are widely used.
  
  
  CONCLUSIONS
  Further research is needed to define the natural history of this disease state, educate patients and clinicians about its distinct natural history and develop informative clinical trial designs suited to this patient population.
authors.affiliation: Department of Medicine and University of California-San Francisco Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California 94143, USA. ryanc@medicine.ucsf.edu
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D008297:Male; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000628:therapy*; D013739:Testosterone / Q000378:metabolism*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D013739:Testosterone; D017430:Prostate-Specific Antigen