title: Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.
abstract: OBJECTIVE
  To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA).
  
  
  RESULTS
  
  
  
  OBJECTIVE
  A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population.
  
  
  METHODS
  The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed.
  
  
  METHODS
  Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation.
  
  
  RESULTS
  An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned.
  
  
  METHODS
  The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative.
  
  
  CONCLUSIONS
  Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. scherh@mskcc.org
authors.forename: Howard I
authors.initials: HI
authors.lastname: Scher
authors.forename: Mario
authors.initials: M
authors.lastname: Eisenberger
authors.forename: Anthony V
authors.initials: AV
authors.lastname: D'Amico
authors.forename: Susan
authors.initials: S
authors.lastname: Halabi
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Small
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kattan
authors.forename: Mack
authors.initials: M
authors.lastname: Roach
authors.forename: Philip
authors.initials: P
authors.lastname: Kantoff
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
authors.forename: David
authors.initials: D
authors.lastname: Agus
authors.forename: Susan F
authors.initials: SF
authors.lastname: Slovin
authors.forename: Glenn
authors.initials: G
authors.lastname: Heller
authors.forename: William Kevin
authors.initials: WK
authors.lastname: Kelly
authors.forename: Paul H
authors.initials: PH
authors.lastname: Lange
authors.forename: Daniel
authors.initials: D
authors.lastname: Petrylak
authors.forename: William
authors.initials: W
authors.lastname: Berg
authors.forename: Celestra
authors.initials: C
authors.lastname: Higano
authors.forename: George
authors.initials: G
authors.lastname: Wilding
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
authors.forename: Alan N
authors.initials: AN
authors.lastname: Partin
authors.forename: Christopher
authors.initials: C
authors.lastname: Logothetis
authors.forename: Howard R
authors.initials: HR
authors.lastname: Soule
mesh_terms: D002986:Clinical Trials as Topic; D004608:Eligibility Determination; D006287:Health Planning Guidelines; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology*; D016896:Treatment Outcome; D014481:United States
chemical_list: D017430:Prostate-Specific Antigen