title: The Phoenix definition of biochemical failure predicts for overall survival in patients with prostate cancer.
abstract: BACKGROUND
  The American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (BF) incorporates backdating, resulting in an artificial flattening of Kaplan-Meier curves and overly favorable estimates when follow-up is short. The nadir + 2 ng/mL (Nadir + 2; Phoenix) definition reduces these artifacts. The objective of the current study was to compare ASTRO and Phoenix BF estimates as determinants of distant metastasis (DM), cause-specific mortality (CSM), and overall mortality (OM).
  
  
  METHODS
  A total of 1831 patients with T1-4N0M0 prostate cancer were treated with external beam radiotherapy (RT) using conventional or three-dimensional conformal methods to at least 60 grays (Gy). The median follow-up was 71 months and the median RT dose was 72 Gy (range, 60-79 Gy). Cox regression models incorporating BF as a time-dependent covariate were used for both univariate and multivariate analyses. Other covariates included in the analyses were T classification, Gleason score, neoadjuvant/adjuvant androgen deprivation, age, RT dose, and pretreatment prostate-specific antigen.
  
  
  RESULTS
  BF was observed in 389 men (21%) using the Phoenix definition and 460 men (25%) using the ASTRO definition. DM was observed in 84 patients (5%), 48 patients (3%) patients died of prostate cancer, and 404 patients (22%) died of any cause. The Phoenix definition of BF was found to be a significant predictor of DM, CSM, and OM, after controlling for other significant covariates. The ASTRO definition was found to be associated with CSM and DM, but not OM.
  
  
  CONCLUSIONS
  The Phoenix definition of BF is a more robust determinant of patient outcome compared with the ASTRO definition. The correlation with mortality, including OM, and the independence of this correlation from the use of neoadjuvant/adjuvant androgen deprivation, supports the use of Nadir + 2 in prostate cancer clinical trials of RT with or without androgen deprivation.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111-2497, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Abramowitz
authors.forename: Tiaynu
authors.initials: T
authors.lastname: Li
authors.forename: Mark K
authors.initials: MK
authors.lastname: Buyyounouski
authors.forename: Eric
authors.initials: E
authors.lastname: Ross
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality* / Q000532:radiotherapy; D012680:Sensitivity and Specificity; D016019:Survival Analysis
chemical_list: D017430:Prostate-Specific Antigen