title: Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy: meta-analysis of radiation therapy oncology group trials.
abstract: OBJECTIVE
  The impact of age on prostate cancer (PCa) outcome has been controversial; therefore, we analyzed the effect of age on overall survival (OS), distant metastasis, prostate cancer-specific death (PCSD), and nonprostate cancer death (NPCD) on patients with locally advanced PCa.
  
  
  METHODS
  Patients who participated in four Radiation Therapy Oncology Group (RTOG) phase III trials, 8531, 8610, 9202, and 9413, were studied. Cox proportional hazards regression was used for OS analysis, and cumulative events analysis with Fine and Gray's regression was used for analyses of metastasis, PCSD, and NPCD.
  
  
  RESULTS
  Median follow-up of 4,128 patients with median age of 70 (range, 43-88 years) was 7.3 years. Most patients had high-risk disease: cT3 to cT4 (54%) and Gleason scores (GS) of 7 (45%) and 8 to 10 (27%). Older age (≤70 vs. >70 years) predicted for decreased OS (10-year rate, 55% vs. 41%, respectively; p<0.0001) and increased NPCD (10-year rate, 28% vs. 46%, respectively; p<0.0001) but decreased metastasis (10-year rate, 27% vs. 20%, respectively; p<0.0001) and PCSD (10-year rate, 18% vs. 14%, respectively; p<0.0001). To account for competing risks, outcomes were analyzed in 2-year intervals, and age-dependent differences in metastasis and PCSD persisted, even in the earliest time periods. When adjusted for other covariates, an age of >70 years remained associated with decreased OS (hazard ratio [HR], 1.56 [95% confidence interval [CI], 1.43-1.70] p<0.0001) but with decreased metastasis (HR, 0.72 [95% CI, 0.63-0.83] p<0.0001) and PCSD (HR, 0.78 [95% CI, 0.66-0.92] p<0.0001). Finally, the impact of the duration of androgen deprivation therapy as a function of age was evaluated.
  
  
  CONCLUSIONS
  These data support less aggressive PCa in older men, independent of other clinical features. While the biological underpinning of this finding remains unknown, stratification by age in future trials appears to be warranted.
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan 48109-5010, USA. dhamm@umich.edu
authors: Daniel A
authors: DA
authors: Hamstra
authors: Kyounghwa
authors: K
authors: Bae
authors: Miljenko V
authors: MV
authors: Pilepich
authors: Gerald E
authors: GE
authors: Hanks
authors: David J
authors: DJ
authors: Grignon
authors: David G
authors: DG
authors: McGowan
authors: Mack
authors: M
authors: Roach
authors: Colleen
authors: C
authors: Lawton
authors: R Jeffrey
authors: RJ
authors: Lee
authors: Howard
authors: H
authors: Sandler
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002423:Cause of Death; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D012044:Regression Analysis; D012307:Risk Factors; D016896:Treatment Outcome