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Original Investigation
October 2015

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

Author Affiliations
  • 1Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 2Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 3Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 4Leonard Davis Institute of Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
  • 5Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania
  • 6Department of Statistics, The Wharton School at the University of Pennsylvania, Philadelphia
  • 7Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
JAMA Oncol. 2015;1(7):897-906. doi:10.1001/jamaoncol.2015.2316
Abstract

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.

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