Long-term biochemical control of prostate cancer after standard or hyper-fractionation: Evidence for different outcomes between low-intermediate and high risk patients

Background and purpose: 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. Materials and 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, alpha/beta 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 alpha/beta 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. (C) 2011 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 101 (2011) 454-459