title: Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer.
abstract: OBJECTIVE
  Although post-radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART.
  
  
  METHODS
  From the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4-12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer-specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease.
  
  
  RESULTS
  When compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042).
  
  
  CONCLUSIONS
  Initiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing.
authors: Department of Urology, Georgetown University Hospital, Washington, DC. Electronic address: keith.kowalczyk@gunet.georgetown.edu.
authors: Keith J
authors: KJ
authors: Kowalczyk
authors: Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Xiangmei
authors: X
authors: Gu
authors: Department of Radiation Oncology, Lank Center for Genitourinary Oncology, Dana Farber Cancer Institute, Boston, MA.
authors: Paul L
authors: PL
authors: Nguyen
authors: Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors: Stuart R
authors: SR
authors: Lipsitz
authors: Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI; Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, Canada.
authors: Quoc-Dien
authors: QD
authors: Trinh
authors: Department of Urology, Georgetown University Hospital, Washington, DC.
authors: John H
authors: JH
authors: Lynch
authors: Department of Radiation Oncology, Georgetown University Hospital, Washington, DC.
authors: Sean P
authors: SP
authors: Collins
authors: Institute of Urologic Oncology, Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors: Jim C
authors: JC
authors: Hu
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D018714:Radiotherapy, Adjuvant / Q000379:methods*; D018426:SEER Program
keywords: Outcomes; Prostate cancer; Radiation therapy; Radical prostatectomy; SEER