title: The impact of comorbidity and PSA doubling time on the risk of death in men experiencing PSA failure following radiation therapy with or with androgen deprivation therapy for unfavorable-risk prostate cancer.
abstract: The optimal management of men with PSA failure following initial prostate cancer (PC) therapy stratified by comorbidity is unknown. We investigated the impact that PSA doubling time (DT) and comorbidity had on the risk of all-cause mortality (ACM), prostate cancer-specific mortality (PCSM) and other-cause mortality (OCM) following PSA failure.
  
  
  
  Between 1995 and 2001, 206 men with unfavorable-risk PC were randomized to receive radiation therapy alone or in combination with 6 months of androgen deprivation therapy (ADT); 108 men experienced PSA failure and formed the study cohort. Cox and Fine-Gray regression analysis was used to determine whether PSA DT was associated with the risk of ACM and PCSM/OCM, respectively, stratified by comorbidity status using a validated metric.
  
  
  
  After a median follow-up of 13.71 years following PSA failure, 81 of the 108 men (75%) died. Longer PSA DT was associated with a decreased risk of PCSM in men with no/minimal (adjusted hazard ratio (AHR) 0.33, 95% confidence interval (CI) 0.17-0.65, P=0.001) and moderate/severe comorbidity (AHR 0.014, 95% CI 0.002-0.129, P=0.0002). However, because of the different contributions of the risk of OCM to risk of ACM within comorbidity subgroups, increasing PSA DT was only associated with a decreased risk of ACM in men with no/minimal (AHR 0.69, 95% CI 0.50-0.96, P=0.03) but not moderate/severe comorbidity (AHR 0.95, 95% CI 0.51-1.78, P=0.87).
  
  
  
  Both the extent of comorbidity and the PSA DT should be taken into consideration when deciding on appropriate management and/or clinical trial eligibility at the time of PSA failure.
authors.affiliation: Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Patel
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, CT, USA.
authors.forename: M-H
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Loffredo
authors.affiliation: Department of Pathology, Miami Baptist Hospital, Miami, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Renshaw
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: P W
authors.initials: PW
authors.lastname: Kantoff
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: D'Amico
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000097:blood*; D002423:Cause of Death; D015897:Comorbidity; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000726:Androgen Antagonists; D014408:Biomarkers, Tumor; D017430:Prostate-Specific Antigen