title: Definition and Validation of "Favorable High-Risk Prostate Cancer": Implications for Personalizing Treatment of Radiation-Managed Patients.
abstract: OBJECTIVE
  To define and validate a classification of favorable high-risk prostate cancer that could be used to personalize therapy, given that consensus guidelines recommend similar treatments for all radiation-managed patients with high-risk disease.
  
  
  METHODS
  We studied 3618 patients with cT1-T3aN0M0 high-risk or unfavorable intermediate-risk prostate adenocarcinoma treated with radiation at a single institution between 1997 and 2013. Favorable high-risk was defined as T1c disease with either Gleason 4 + 4 = 8 and prostate-specific antigen <10 ng/mL or Gleason 6 and prostate-specific antigen >20 ng/mL. Competing risks regression was used to determine differences in the risk of prostate cancer-specific mortality (PCSM) after controlling for baseline factors and treatment. Our results were validated in a cohort of 13,275 patients using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database.
  
  
  RESULTS
  Patients with favorable high-risk disease had significantly better PCSM than other men with high-risk disease (adjusted hazard ratio [AHR] 0.42, 95% confidence interval [CI] 0.18-0.996, P=.049) and similar PCSM as men with unfavorable intermediate-risk disease (AHR 1.17, 95% CI 0.50-2.75, P=.710). We observed very similar results within the SEER-Medicare cohort (favorable high-risk vs other high-risk: AHR 0.21, 95% CI 0.11-0.41, P<.001; favorable high-risk vs unfavorable intermediate-risk: AHR 0.67, 95% CI 0.33-1.36, P=.268).
  
  
  CONCLUSIONS
  Patients with favorable high-risk prostate cancer have significantly better PCSM than other patients with high-risk disease and similar PCSM as those with unfavorable intermediate-risk disease, who are typically treated with shorter-course androgen deprivation therapy. This new classification system may allow for personalization of treatment within high-risk disease, such as consideration of shorter-course androgen deprivation therapy for favorable high-risk disease.
authors.affiliation: Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Vinayak
authors.initials: V
authors.lastname: Muralidhar
authors.affiliation: Department of Statistics, University of Connecticut, Storrs, Connecticut.
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Center for Surgery and Public Health, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
authors.forename: Gally
authors.initials: G
authors.lastname: Reznor
authors.affiliation: Prostate Cancer Foundation of Chicago, Westmont, Illinois.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Moran
authors.affiliation: Prostate Cancer Foundation of Chicago, Westmont, Illinois.
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Braccioforte
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Clair J
authors.initials: CJ
authors.lastname: Beard
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.affiliation: Department of Radiation Oncology, M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hoffman
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Martin
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Sweeney
authors.affiliation: Department of Urology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: pnguyen@LROC.harvard.edu.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Nguyen
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods; D016001:Confidence Intervals; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D057285:Precision Medicine; D011379:Prognosis; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000145:classification* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D018570:Risk Assessment / Q000379:methods; D018426:SEER Program
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen