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

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.

Fig. 1

Prevalence and cumulative incidence of rectal bleeding. (A, B) RMH; (C, D) LENT/SOM. Obj = objective; Std = standard arm, 64 Gy; Esc = escalated arm, 74 Gy; m = month; gr = grade; pre-H = prehormonal therapy; pre-RT = preradiation therapy.

Fig. 2

Prevalence and cumulative incidence of diarrhea. (A, B) RTOG; (C, D) RMH; (E, F) LENT/SOM; (G, H) UCLA-PCI; (I, J) abdominal pain, UCLA-PCI. Subj = subjective; Std = standard arm; Esc = escalated arm; m = month; gr = grade; pre-H = prehormonal therapy; pre-RT = preradiation therapy.

Fig. 2

Prevalence and cumulative incidence of diarrhea. (A, B) RTOG; (C, D) RMH; (E, F) LENT/SOM; (G, H) UCLA-PCI; (I, J) abdominal pain, UCLA-PCI. Subj = subjective; Std = standard arm; Esc = escalated arm; m = month; gr = grade; pre-H = prehormonal therapy; pre-RT = preradiation therapy.

Fig. 3

Prevalence and cumulative incidence of proctitis. (A, B) RTOG; (C, D) rectal urgency, UCLA-PCI. Std = standard arm; Esc = escalated arm; m = month; gr = grade; pre-H = prehormonal therapy; pre-RT = preradiation therapy.

Fig. 4

Prevalence and cumulative incidence of patient distress and difficulties. (A, B) Bowel distress, UCLA-PCI; (C, D) problems with bowel habits, UCLA-PCI; (E, F) trouble moving bowels, FACT-P. Std = standard arm; Esc = escalated arm; m = month; gr = grade; pre-H = prehormonal therapy; pre-RT = preradiation therapy.