title: An international multicenter study evaluating the impact of an alternative biochemical failure definition on the judgment of prostate cancer risk.
abstract: OBJECTIVE
  To evaluate the impact of an alternative biochemical failure (bF) definition on the performance of existing plus de novo prognostic models.
  
  
  METHODS
  The outcomes data of 1,458 Australian and 703 Canadian men treated with external-beam radiation monotherapy between 1993 and 1997 were analyzed using a lowest prostate-specific antigen (PSA) level to date plus 2 ng/mL (L + 2) bF definition. Two existing prognostic models were scrutinized using discrimination (Somers Dxy [SDxy]) and calibration indices. Alternative prognostic models were also created using recursive partitioning analysis (RPA) and multivariate nomogram methods for comparison.
  
  
  RESULTS
  Discrimination of bF was improved using the L + 2 definition compared with the American Society for Therapeutic Radiology and Oncology (ASTRO) definition using both the three-level risk model (SDxy 0.30 and 0.22, respectively) or the nomogram (SDxy 0.35 and 0.27, respectively). Both existing prognostic models showed only modest calibration accuracy. Using RPA, five distinct risk groups were identified based primarily on Gleason score (GS) and all subsequent divisions based on PSA. All GS 7-10 tumors were intermediate or high risk. This model and the developed nomogram showed improved discrimination over the existing models as well as accurate calibration against the Canadian data, apart from the 30-50% failure region.
  
  
  CONCLUSIONS
  The L + 2 definition of bF provides improved capacity for discrimination of failure risk. New prognostic models based on this endpoint have overall statistical performance superior to those based on the ASTRO consensus definition but continue to have unreliable discrimination in the intermediate-risk region.
authors.affiliation: Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. scott.williams@petermac.org
authors.forename: Scott G
authors.initials: SG
authors.lastname: Williams
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Duchesne
authors.forename: N Kumar
authors.initials: NK
authors.lastname: Gogna
authors.forename: Jeremy L
authors.initials: JL
authors.lastname: Millar
authors.forename: Tom
authors.initials: T
authors.lastname: Pickles
authors.forename: Gary R
authors.initials: GR
authors.lastname: Pratt
authors.forename: Sandra
authors.initials: S
authors.lastname: Turner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002138:Calibration; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009367:Neoplasm Staging; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000532:radiotherapy*; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D017211:Treatment Failure
chemical_list: D017430:Prostate-Specific Antigen