title: Dose-Escalated Irradiation and Overall Survival in Men With Nonmetastatic Prostate Cancer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Anusha
authors.initials: A
authors.lastname: Kalbasi
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia3Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Abigail
authors.initials: A
authors.lastname: Berman
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia4Leonard Davis Institute of Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Samuel
authors.initials: S
authors.lastname: Swisher-McClure
authors.affiliation: Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.
authors.forename: Marc
authors.initials: M
authors.lastname: Smaldone
authors.affiliation: Division of Urologic Oncology, Department of Surgery, Fox Chase Cancer Center, Temple University Health System, Philadelphia, Pennsylvania.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Uzzo
authors.affiliation: Leonard Davis Institute of Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia6Department of Statistics, The Wharton School at the University of Pennsylvania, Philadelphia.
authors.forename: Dylan S
authors.initials: DS
authors.lastname: Small
authors.affiliation: Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.affiliation: Department of Radiation Oncology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia7Department of Medical Ethics and Health Policy, Perelman School of Medicine at the University of Pennsylvania, Philadelphia.
authors.forename: Justin E
authors.initials: JE
authors.lastname: Bekelman
mesh_terms: D057186:Comparative Effectiveness Research; D016208:Databases, Factual; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D057216:Propensity Score; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome