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

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 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 P P  = .54). For every incremental increase of about 2 Gy in dose, there was a 7.8% (95% CI, 5.4%-10.2%; P P 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.