title: Long-term biochemical control of prostate cancer after standard or hyper-fractionation: evidence for different outcomes between low-intermediate and high risk patients.
abstract: OBJECTIVE
  To report the long-term biochemical control of a non-randomized trial comparing standard (STD) and hyper-fractionated (HFX) radiation schedules for prostate cancer treatment.
  
  
  METHODS
  Between 1993 and 2003, 370 patients entered the study; 330/370 (STD: 179; HFX: 151) were evaluable for current analysis. Median doses were 79.2 Gy and 74 Gy for HFX (1.2 Gy/fr, two daily fractions) and STD (2 Gy/fr), respectively; median follow-up was 7.5 yr. The two regimens were compared in terms of biochemical relapse-free survival (according to ASTRO definition, bRFS) by univariate (log-rank test) and multivariate analyses (Cox regression hazard model). Based on published relationships between EQD2 and 5-yr biochemical control, α/β values for each subgroup could be estimated.
  
  
  RESULTS
  7.5 yr bRFS were 53.4% (± 4.4%, 95% CI) and 65.4% (± 4.0%) for HFX and STD, respectively (p=0.13); HFX was associated with a poorer outcome in NCCN low+intermediate patients (7.5 yr bRFS: 56.6% vs 73.5%, p=0.048) while no differences were seen for high-risk patients (7.5 yr bRFS: 44.1% vs 45.3%). Multivariate analysis revealed that NCCN risk grouping (high vs low+intermediate; OR: 0.59, p=0.009) and age (< vs ≥ 70 yr; OR: 0.67, p=0.03) were the main predictors of worse bRFS. In the subgroups of low+intermediate-risk patients < 70 yr, the poorer outcome of HFX was more evident (7.5 yr bRFS: 47.1% vs 70.9%, p=0.078) while no difference was seen for older patients (7.5 yr bRFS: 69.4% vs 72.0%, p=0.76). Our α/β estimates differ between low+intermediate-risk and high-risk patients.
  
  
  CONCLUSIONS
  The bRFS long-term results of this non-randomized trial are consistent with different sensitivities to fractionation depending on NCCN risk grouping. The impact of age on the outcome of HFX for younger low+intermediate patients is consistent with an incomplete repair effect in older patients.
authors.affiliation: Prostate Program, Scientific Director's Office, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.forename: Alan E
authors.initials: AE
authors.lastname: Nahum
authors.forename: Tiziana
authors.initials: T
authors.lastname: Magnani
authors.forename: Corrado
authors.initials: C
authors.lastname: Italia
authors.forename: Angelo
authors.initials: A
authors.lastname: Lanceni
authors.forename: Paolo
authors.initials: P
authors.lastname: Montanaro
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rancati
authors.forename: Barbara
authors.initials: B
authors.lastname: Avuzzi
authors.forename: Claudio
authors.initials: C
authors.lastname: Fiorino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011471:Prostatic Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D012306:Risk; D016896:Treatment Outcome