Dose-Escalated Irradiation and Overall Survival in Men With Nonmetastatic Prostate Cancer

JAMA Oncol. 2015 Oct;1(7):897-906. doi: 10.1001/jamaoncol.2015.2316.


Importance: In 5 published randomized clinical trials, dose-escalated external-beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, scarce evidence addresses whether dose escalation improves overall survival.

Objective: To examine the association between dose-escalated EBRT and overall survival among men with nonmetastatic prostate cancer.

Design, setting, and participants: We conducted a retrospective, nonrandomized comparative effectiveness study of dose-escalated vs standard-dose EBRT for prostate cancer diagnosed from 2004 to 2006 using the National Cancer Database (NCDB), which includes data from patients treated at Commission on Cancer-accredited community, academic, and comprehensive cancer facilities. Three cohorts were evaluated: men with low-risk (n = 12,229), intermediate-risk (n = 16,714), or high-risk (n = 13,538) prostate cancer.

Exposures: We categorized patients in each risk cohort into 2 treatment groups: standard-dose (from 68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT (1 Gy = 100 rad).

Main outcomes and measures: We compared overall survival between treatment groups in each analytic cohort using Cox proportional hazard models with an inverse probability weighted propensity score (IPW-PS) approach. In secondary analyses, we evaluated dose response for survival.

Results: Dose-escalated EBRT was associated with improved survival in the intermediate-risk (IPW-PS adjusted hazard ratio [HR], 0.84; 95% CI, 0.80-0.88; P < .001) and high-risk groups (HR, 0.82; 95% CI, 0.78-0.85; P < .001) but not the low-risk group (HR, 0.98; 95% CI, 0.92-1.05; P = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P < .001) and 6.3% (95% CI, 3.3%-9.1%; P < .001) reduction in the hazard of death for intermediate- and high-risk patients, respectively.

Conclusions and relevance: Dose-escalated EBRT is associated with improved overall survival in men with intermediate- and high-risk prostate cancer but not low-risk prostate cancer. These results add to the evidence questioning aggressive local treatment strategies in men with low-risk prostate cancer but supporting such treatment in men with greater disease severity.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Comparative Effectiveness Research
  • Databases, Factual
  • Dose-Response Relationship, Radiation
  • Humans
  • Male
  • Multivariate Analysis
  • Propensity Score
  • Proportional Hazards Models
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy Dosage*
  • Radiotherapy, Intensity-Modulated / adverse effects
  • Radiotherapy, Intensity-Modulated / methods*
  • Radiotherapy, Intensity-Modulated / mortality
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome