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Purpose: To test the hypothesis that increased acute toxicity, measured using subdomains reflective of epithelial cell damage, will be associated with reduced late biochemical failure, as a surrogate for tumor radiosensitivity.Methods and Materials: The study design was retrospective, with discovery and validation cohorts involving routinely collected data. Eligible patients had prostate cancer, underwent radiation therapy with curative intent, and had acute toxicity assessed prospectively. The discovery cohort was from a single institution. Genitourinary and gastrointestinal acute toxicity related to epithelial cell damage (hematuria, dysuria, proctitis, or mucus) were related to freedom from late biochemical failure (FFBF; nadir + 2). The validation cohort was from two separate institutions.Results: In all, 503 patients were included in the discovery cohort and 658 patients in the validation cohort. In the validation cohort, patients with acute radiation toxicity reflecting epithelial damage had a longer FFBF on both univariate (hazard ratio [HR] 0.37; P = .004) and multivariate (HR 0.45; P = .035) analysis. The impact of acute toxicity on late FFBF seemed to be greater in patients treated with androgen deprivation (HR 0.19) than in those without (HR 0.48).Conclusion: Patients reporting acute radiation toxicity reflective of epithelial cell damage during definitive radiation therapy for prostate cancer have significantly longer FFBF, consistent with an underlying genetic link between normal tissue and tumor radiosensitivity. [ABSTRACT FROM AUTHOR]

Purpose: Outcome data on radiation therapy for prostate cancer in an elderly population are sparse. The CHHiP (Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer) trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.Methods and Materials: CHHiP participants received 3 to 6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74 Gy in 37 fractions (conventional fractionation), 60 Gy in 20 fractions, or 57 Gy in 19 fractions. Toxicity was assessed using clinician-reported outcome (CRO) and patient-reported outcome questionnaires. Participants were categorized as aged < 75 years or ≥ 75 years. Outcomes were compared by age group.Results: Of 3216 patients, 491 (15%) were aged ≥ 75 years. There was no difference in biochemical or clinical failure rates between the groups aged < 75 years and ≥ 75 years for any of the fractionation schedules. In the group aged ≥ 75 years, biochemical or clinical failure-free rates favored hypofractionation, and at 5 years, they were 84.7% for 74 Gy, 91% for 60 Gy, and 87.7% for 57 Gy. The incidence of CRO (grade 3) acute bowel toxicity was 2% in both age groups. The incidence of grade 3 acute bladder toxicity was 8% in patients aged < 75 years and 7% in those aged ≥ 75 years. The 5-year cumulative incidence of CRO grade ≥ 2 late bowel side effects was similar in both age groups. However, in the group aged ≥ 75 years, there was a suggestion of a higher cumulative incidence of bowel bother (small or greater) with 60 Gy compared with 74 Gy and 57 Gy. Patient-reported bladder bother was slightly higher in the group aged ≥ 75 years than the group aged < 75 years, and there was a suggestion of a lower cumulative incidence of bladder bother with 57 Gy compared with 74 Gy and 60 Gy in patients aged ≥ 75 years, which was not evident in those aged < 75 years.Conclusions: Hypofractionated radiation therapy appears to be well tolerated and effective in men aged ≥ 75 years. The 57-Gy schedule has potential advantages in that it may moderate long-term side effects without compromising treatment efficacy in this group. [ABSTRACT FROM AUTHOR]