title: Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.
abstract: OBJECTIVE
  To update eligibility and outcome measures in trials that evaluate systemic treatment for patients with progressive prostate cancer and castrate levels of testosterone.
  
  
  METHODS
  A committee of investigators experienced in conducting trials for prostate cancer defined new consensus criteria by reviewing previous criteria, Response Evaluation Criteria in Solid Tumors (RECIST), and emerging trial data.
  
  
  RESULTS
  The Prostate Cancer Clinical Trials Working Group (PCWG2) recommends a two-objective paradigm: (1) controlling, relieving, or eliminating disease manifestations that are present when treatment is initiated and (2) preventing or delaying disease manifestations expected to occur. Prostate cancers progressing despite castrate levels of testosterone are considered castration resistant and not hormone refractory. Eligibility is defined using standard disease assessments to authenticate disease progression, prior treatment, distinct clinical subtypes, and predictive models. Outcomes are reported independently for prostate-specific antigen (PSA), imaging, and clinical measures, avoiding grouped categorizations such as complete or partial response. In most trials, early changes in PSA and/or pain are not acted on without other evidence of disease progression, and treatment should be continued for at least 12 weeks to ensure adequate drug exposure. Bone scans are reported as "new lesions" or "no new lesions," changes in soft-tissue disease assessed by RECIST, and pain using validated scales. Defining eligibility for prevent/delay end points requires attention to estimated event frequency and/or random assignment to a control group.
  
  
  CONCLUSIONS
  PCWG2 recommends increasing emphasis on time-to-event end points (ie, failure to progress) as decision aids in proceeding from phase II to phase III trials. Recommendations will evolve as data are generated on the utility of intermediate end points to predict clinical benefit.
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Sidney Kimmel Center for Prostate and Urologic Cancers, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065, USA. byczekb@mskcc.org
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Ian
authors.initials: I
authors.lastname: Tannock
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Celestia
authors.initials: C
authors.lastname: Higano
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Bubley
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrylak
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.forename: Ethan
authors.initials: E
authors.lastname: Basch
authors.forename: William Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: William D
authors.initials: WD
authors.lastname: Figg
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Tomasz M
authors.initials: TM
authors.lastname: Beer
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Alison
authors.initials: A
authors.lastname: Martin
authors.forename: Maha
authors.initials: M
authors.lastname: Hussain
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000473:pathology* / Q000628:therapy; D002986:Clinical Trials as Topic / Q000592:standards*; D018450:Disease Progression; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care / Q000592:standards; D018579:Patient Selection; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy; D012107:Research Design / Q000592:standards*; D013739:Testosterone / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D013739:Testosterone; D017430:Prostate-Specific Antigen