Acute Epithelial Toxicity Is Prognostic for Improved Prostate Cancer Response to Radiation Therapy: A Retrospective, Multicenter, Cohort Study

Research output: Contribution to journalArticle

  • External authors:
  • Thomas Eade
  • Alan Pollack
  • Matthew Abramowitz
  • Felix M. Chinea
  • Linxin Guo
  • Jason Kennedy
  • Sandra Louw
  • George Hruby
  • Andrew Kneebone

Abstract

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.

Bibliographical metadata

Original languageEnglish
Pages (from-to)957-963
JournalInternational Journal of Radiation: Oncology - Biology - Physics
Volume101
Issue number4
Early online date11 Apr 2018
DOIs
Publication statusPublished - 15 Jul 2018