title: Impact of ultrahigh baseline PSA levels on biochemical and clinical outcomes in two Radiation Therapy Oncology Group prostate clinical trials.
abstract: OBJECTIVE
  To assess ultrahigh (UH; prostate-specific antigen [PSA] levels ≥50 ng/ml) patient outcomes by comparison to other high-risk patient outcomes and to identify outcome predictors.
  
  
  METHODS
  Prostate cancer patients (PCP) from two Phase III Radiation Therapy Oncology Group clinical trials (studies 9202 and 9413) were divided into two groups: high-risk patients with and without UH baseline PSA levels. Predictive variables included age, Gleason score, clinical T stage, Karnofsky performance score, and treatment arm. Outcomes included overall survival (OS), distant metastasis (DM), and biochemical failure (BF). Unadjusted and adjusted hazard ratios (HRs) were calculated using either the Cox or Fine and Gray's regression model with associated 95% confidence intervals (CI) and p values.
  
  
  RESULTS
  There were 401 patients in the UH PSA group and 1,792 patients in the non-UH PSA PCP group of a total of 2,193 high-risk PCP. PCP with UH PSA were found to have inferior OS (HR, 1.19; 95% CI, 1.02-1.39, p = 0.02), DM (HR, 1.51; 95% CI, 1.19-1.92; p = 0.0006), and BF (HR, 1.50; 95% CI, 1.29-1.73; p < 0.0001) compared to other high-risk PCP. In the UH cohort, PSA level was found to be a significant factor for the risk of DM (HR, 1.01; 95% CI, 1.001-1.02) but not OS and BF. Gleason grades of 8 to 10 were found to consistently predict for poor OS, DM, and BF outcomes (with HR estimates ranging from 1.41-2.36) in both the high-risk cohort and the UH cohort multivariable analyses.
  
  
  CONCLUSIONS
  UH PSA levels at diagnosis are related to detrimental changes in OS, DM, and BF. All three outcomes can be modeled by various combinations of all predictive variables tested.
authors.affiliation: Department of Oncology, University of Western Ontario, London, Ontario, Canada. george.rodrigues@lhsc.on.ca
authors.forename: George
authors.initials: G
authors.lastname: Rodrigues
authors.forename: Kyounghwa
authors.initials: K
authors.lastname: Bae
authors.forename: Mack
authors.initials: M
authors.lastname: Roach
authors.forename: Colleen
authors.initials: C
authors.lastname: Lawton
authors.forename: Bryan
authors.initials: B
authors.lastname: Donnelly
authors.forename: David
authors.initials: D
authors.lastname: Grignon
authors.forename: Gerald
authors.initials: G
authors.lastname: Hanks
authors.forename: Arthur
authors.initials: A
authors.lastname: Porter
authors.forename: Herbert
authors.initials: H
authors.lastname: Lepor
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D006801:Humans; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D012044:Regression Analysis; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen