title: Radiotherapy doses of 80 Gy and higher are associated with lower mortality in men with Gleason score 8 to 10 prostate cancer.
abstract: OBJECTIVE
  Men with Gleason score (GS) 8-10 prostate cancer (PCa) are assumed to have a high risk of micrometastatic disease at presentation. However, local failure is also a major problem. We sought to establish the importance of more aggressive local radiotherapy (RT) to ≥80 Gy.
  
  
  METHODS
  There were 226 men treated consecutively with RT ± ADT from 1988 to 2002 for GS 8-10 PCa. Conventional, three-dimensional conformal or intensity-modulated (IM) RT was used. Radiation dose was divided into three groups: (1) <75 Gy (n = 50); (2) 75-79.9 Gy (n = 60); or (3) ≥80 Gy (n = 116). The endpoints examined included biochemical failure (BF; nadir + 2 definition), distant metastasis (DM), cause-specific mortality, and overall mortality (OM).
  
  
  RESULTS
  Median follow-up was 66, 71, and 58 months for Groups 1, 2, and 3. On Fine and Gray's competing risk regression analysis, significant predictors of reduced BF were RT dose ≥80 Gy (p = 0.011) and androgen deprivation therapy duration ≥24 months (p = 0.033). In a similar model of DM, only RT dose ≥80 Gy was significant (p = 0.007). On Cox regression analysis, significant predictors of reduced OM were RT dose ≥80 Gy (p = 0.035) and T category (T3/4 vs. T1, p = 0.041). Dose was not a significant determinant of cause-specific mortality. Results for RT dose were similar in a model with RT dose and ADT duration as continuous variables.
  
  
  CONCLUSIONS
  The results indicate that RT dose escalation to ≥80 Gy is associated with lower risks of BF, DM, and OM in men with GS 8-10 PCa, independently of androgen deprivation therapy.
authors.affiliation: Department of Radiation Oncology, Cooper University Hospital, Camden, NJ, USA.
authors.forename: Niraj
authors.initials: N
authors.lastname: Pahlajani
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Ruth
authors.forename: Mark K
authors.initials: MK
authors.lastname: Buyyounouski
authors.forename: David Y T
authors.initials: DY
authors.lastname: Chen
authors.forename: Eric M
authors.initials: EM
authors.lastname: Horwitz
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Hanks
authors.forename: Robert A
authors.initials: RA
authors.lastname: Price
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use; D023381:Endpoint Determination; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011467:Prostate / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods; D012044:Regression Analysis; D012669:Seminal Vesicles / Q000528:radiation effects; D016019:Survival Analysis
chemical_list: D000726:Androgen Antagonists