title: Update of Dutch multicenter dose-escalation trial of radiotherapy for localized prostate cancer.
abstract: OBJECTIVE
  To update the analysis of the Dutch dose-escalation trial of radiotherapy for prostate cancer.
  
  
  METHODS
  A total of 669 patients with localized prostate cancer were randomly assigned to receive 68 or 78 Gy. The patients were stratified by age, institution, use of neoadjuvant or adjuvant hormonal therapy, and treatment group. The primary endpoint was freedom from failure (FFF), with failure defined as clinical or biochemical failure. Two definitions of biochemical failure were used: the American Society for Therapeutic Radiology and Oncology definition (three consecutive increases in prostate-specific antigen level) and the Phoenix definition (nadir plus 2 microe secondary endpoints were freedom from clinical failure, overall survival, and genitourinary and gastrointestinal toxicity.
  
  
  RESULTS
  After a median follow-up of 70 months, the FFF using the American Society for Therapeutic Radiology and Oncology definition was significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 54% vs. 47%, respectively; p = 0.04). The FFF using the Phoenix definition was also significantly better in the 78-Gy arm than in the 68-Gy arm (7-year FFF rate, 56% vs. 45%, respectively; p = 0.03). However, no differences in freedom from clinical failure or overall survival were observed. The incidence of late Grade 2 or greater genitourinary toxicity was similar in both arms (40% and 41% at 7 years; p = 0.6). However, the cumulative incidence of late Grade 2 or greater gastrointestinal toxicity was increased in the 78-Gy arm compared with the 68-Gy arm (35% vs. 25% at 7 years; p = 0.04).
  
  
  CONCLUSIONS
  The results of our study have shown a statistically significant improvement in FFF in prostate cancer patients treated with 78 Gy but with a greater rate of late gastrointestinal toxicity.
authors.affiliation: Erasmus Medical Centre-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. a.al-mamgani@erasmusmc.nl
authors.forename: Abrahim
authors.initials: A
authors.lastname: Al-Mamgani
authors.forename: Wim L J
authors.initials: WL
authors.lastname: van Putten
authors.forename: Wilma D
authors.initials: WD
authors.lastname: Heemsbergen
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
authors.forename: Annerie
authors.initials: A
authors.lastname: Slot
authors.forename: Michel F H
authors.initials: MF
authors.lastname: Dielwart
authors.forename: Luca
authors.initials: L
authors.lastname: Incrocci
authors.forename: Joos V
authors.initials: JV
authors.lastname: Lebesque
mesh_terms: D000368:Aged; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology* / Q000517:prevention & control*; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence; D011471:Prostatic Neoplasms / Q000453:epidemiology* / Q000532:radiotherapy*; D011829:Radiation Dosage; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors