Proctitis 1 Week after Stereotactic Body Radiation Therapy for Prostate Cancer: Implications for Clinical Trial Design

Abstract

Background: Proctitis following prostate cancer radiation therapy is a primary determinant of quality of life (QOL). While previous studies have assessed acute rectal morbidity at 1 month after stereotactic body radiotherapy (SBRT), little data exist on the prevalence and severity of rectal morbidity within the first week following treatment. This study reports the acute bowel morbidity 1 week following prostate SBRT.

Materials and methods: Between May 2013 and August 2014, 103 patients with clinically localized prostate cancer were treated with 35-36.25 Gy in five fractions using robotic SBRT delivered on a prospective clinical trial. Bowel toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAEv.4). Bowel QOL was assessed using the EPIC-26 questionnaire bowel domain at baseline, 1 week, 1 month, and 3 months. Time-dependent changes in bowel symptoms were statistically compared using the Wilcoxon signed-rank test. Clinically significant change was assessed by the minimally important difference (MID) in EPIC score. This was defined as a change of 1/2 standard deviation (SD) from the baseline score.

Results: One-hundred and three patients with a minimum of 3 months of follow-up were analyzed. The cumulative incidence of acute grade 2 gastrointestinal (GI) toxicity was 23%. There were no acute ≥ grade 3 bowel toxicities. EPIC bowel summary scores maximally declined at 1 week after SBRT (-13.9, p < 0.0001) before returning to baseline at 3 months after SBRT (+0.03, p = 0.94). Prior to treatment, 4.9% of men reported that their bowel bother was a moderate to big problem. This increased to 28.4% (p < 0.0001) 1 week after SBRT and returned to baseline at 3 months after SBRT (0.0%, p = 0.66). Only the bowel summary and bowel bother score declines at 1 week met the MID threshold for clinically significant change.

Conclusion: The rate and severity of acute proctitis following prostate SBRT peaked at 1 week after treatment and returned to baseline by 3 months. Toxicity assessment at 1 week can therefore minimize recall bias and should aid in the design of future clinical trials focused on accurately capturing and minimizing acute morbidity following SBRT.

Keywords: CyberKnife; EPIC; SBRT; prostate cancer; recall period; symptom management trial; time point.

Figure 1

Average EPIC bowel summary scores (baseline and following SBRT; question 6A-E of EPIC-26). Dashed lines represent the minimally important difference (MID) defined as the threshold for clinically significant change in scores (1/2 SD above and below the baseline). Higher EPIC score values (range 0–100) indicate a more satisfactory health-related QOL. Vertical lines at each time point represent 95% confidence interval.

Figure 2

Overall bowel bother score (baseline and following SBRT; question 7 of EPIC-26). Dashed lines represent the minimally important difference (MID) defined as the threshold for clinically significant change in scores (1/2 SD above and below the baseline). Higher EPIC score values (range 0–100) indicate a more satisfactory health-related QOL. Vertical lines at each time point represent 95% confidence interval.

Figure 3

Radar plots showing the distribution of individual bowel symptoms following SBRT for prostate cancer. Higher EPIC score values (range 0–100) indicate a more satisfactory health-related QOL. Points farther out from the center indicate higher levels of bother with a given symptom.