title: Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy.
abstract: OBJECTIVE
  Modern outcomes of high-dose external beam radiotherapy (EBRT) with androgen deprivation therapy (ADT) for high-risk (HR) prostate cancer are not well described.
  
  
  METHODS
  We identified 585 patients who met HR criteria by 2010 National Comprehensive Cancer Network guidelines, who were treated with EBRT consisting of ≥74 Gy from 1996 to 2008 at Cleveland Clinic, of whom 95% received ADT. We analyzed biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).
  
  
  RESULTS
  The median EBRT dose was 78 Gy, and median ADT duration was 6 months. At 10 years, the bRFS was 50.2%, the DMFS was 71.6%, and the PCSM was 14.4%. On multivariate analysis, significant predictors of bRFS were biopsy Gleason score (bGS) of 8 to 10, stage T3, and prostate-specific antigen (PSA) concentration; predictors of DMFS were bGS of 8 to 10 and stage T3; the only predictor of PCSM was bGS of 8 to 10. The duration of ADT was not predictive of any endpoint. We identified an unfavorable high-risk (UHR) group of stage T1-T2 tumors consisting of bGS of 8 with PSA of >10 ng/ml or bGS of 9 to 10 with any PSA level; the remaining clinically localized cancers comprised the favorable high-risk (FHR) group. Comparing FHR, UHR, and stage T3 groups, the DMFS rates were 81.4%, 57.8%, and 59.1% (p < 0.0001), and the PCSM rates were 7.5%, 28.4%, and 20.6% at 10 years, respectively (p = 0.006).
  
  
  CONCLUSIONS
  A bGS of 8 to 10 is the strongest predictor of bRFS, DMFS, and PCSM after high-dose EBRT with ADT. The duration of ADT did not correlate with outcome. Future studies should account for the heterogeneity in HR prostate cancer.
authors.affiliation: Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA. tendulr@ccf.org
authors.forename: Rahul D
authors.initials: RD
authors.lastname: Tendulkar
authors.forename: Chandana A
authors.initials: CA
authors.lastname: Reddy
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Stephans
authors.forename: Jay P
authors.initials: JP
authors.lastname: Ciezki
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Arul
authors.initials: A
authors.lastname: Mahadevan
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Kupelian
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D002423:Cause of Death; D003131:Combined Modality Therapy / Q000379:methods; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011878:Radiotherapy / Q000379:methods; D011879:Radiotherapy Dosage; D012306:Risk
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen