Late gastrointestinal toxicity after dose-escalated conformal radiotherapy for early prostate cancer: results from the UK Medical Research Council RT01 trial (ISRCTN47772397)

Int J Radiat Oncol Biol Phys. 2010 Jul 1;77(3):773-83. doi: 10.1016/j.ijrobp.2009.05.052. Epub 2009 Oct 14.

Abstract

Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects.

Methods and materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires.

Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade >or=2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade >or=2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade >or=2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively.

Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diarrhea / epidemiology
  • Diarrhea / etiology*
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / etiology*
  • Humans
  • Incidence
  • Male
  • Neoplasm Staging
  • Proctitis / epidemiology
  • Proctitis / etiology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy Dosage
  • Radiotherapy, Conformal / adverse effects*
  • Radiotherapy, Conformal / methods
  • Rectal Diseases / epidemiology
  • Rectal Diseases / etiology*
  • Rectum / radiation effects
  • United Kingdom

Associated data

  • ISRCTN/ISRCTN47772397