Impact of dose-escalated radiation on overall survival in men with nonmetastatic prostate cancer.

Abstract

28 Background: Infive publishedRCTs, dose-escalated external beam radiation therapy (EBRT) for prostate cancer resulted in improved biochemical and local control. However, the question of whether dose escalation improves overall survival (OS) remains unanswered. We examined OS among men with non-metastatic prostate cancer undergoing EBRT in the modern era. Methods: Using the National Cancer Database (NCDB), we conducted non-randomized comparative effectiveness studies of dose-escalated versus standard-dose EBRT in men diagnosed from 2004-2006 in three analytic cohorts defined by NCCN risk category: low- (N=12,848), intermediate- (N=14,966) or high-risk (N=14,587) prostate cancer. We categorized patients in each risk cohort into 2 treatment groups: standard-dose (68.4 Gy to <75.6 Gy) or dose-escalated (≥75.6 Gy to 90 Gy) EBRT. The primary outcome was time to death from any cause, measured from diagnosis to NCDB date of death or end of follow-up (December 31, 2011). We compared OS between treatment groups in the three analytic cohorts using Cox proportional hazard models. Inverse probability weighted propensity score methods were used to balance differences between treatment groups in age, race, year of diagnosis, AJCC T- and N-stage, PSA, Gleason score, androgen deprivation therapy, IMRT use, comorbid disease, income, insurance, urban/rural location, facility type and facility volume. In secondary analyses, we evaluated dose response for survival by categorizing dose in approximately 2 Gy increments. Results: Median follow up for survivors was between 73 and 74 months in all three risk cohorts. Dose-escalated EBRT was associated with improved survival in the intermediate-risk (adjusted HR 0.81, 95% CI 0.77 and 0.85, p<0.0001) and high-risk groups (aHR 0.85, 95% CI 0.81 and 0.89, p<0.0001), but not the low-risk group (aHR 0.99, 95% CI 0.92-1.06, p=0.803). For every incremental ~2Gy increase in dose, there was a 9% (95% CI 6% – 11%, p<0.0001) and 7% (95% CI 3% - 10%, p=0.004) reduction in the hazard of death for intermediate- and high-risk patients, respectively. Conclusions: Dose-escalated EBRT is associated with improved survival in men with intermediate- and high-risk, but not low-risk, prostate cancer.