Short-term safety of adjuvant chemoradiotherapy after local resection for patients with high-risk submucosal invasive rectal cancer: a single-arm, multicenter phase II trial

BACKGROUND: Surgery is recommended for patients with high-risk submucosal invasive rectal cancer (SM-RC) after local resection but affects the quality of life due to stoma placement or impaired anal function; therefore, alternative treatment approaches are needed to prevent local metastasis. The purpose of this study was to assess the short-term safety of adjuvant chemoradiotherapy with capecitabine in patients with high-risk submucosal invasive rectal cancer after local resection. METHODS: This single-arm, multicenter, phase II trial included patients undergoing local resection for high-risk submucosal invasive rectal cancer within 12 weeks prior to enrollment. High-risk submucosal invasive rectal cancer was defined as the presence of at least one of the following factors: poor differentiation of adenocarcinoma, submucosal invasion depth > 1 mm, presence of lymphovascular invasion and grade-2 or -3 tumour budding. Protocol treatment comprised 45.0 Gy radiotherapy with conventional fractionation and 1650 mg/m(2) capecitabine given twice daily until radiotherapy completion. The primary endpoint was treatment completion rate with an expected rate of 95% and a threshold of 80%. RESULTS: Twenty-nine patients from six institutions were enrolled between May 2015 and February 2018. One patient was ineligible. Twenty-three patients completed treatment, with a completion rate of 82% (80% confidence interval, 69–91%); the remaining five patients completed treatment with protocol deviation. The median relative dose intensity of capecitabine was 100% (range, 58–100%). Common adverse events included radiation dermatitis (54%), anal pain (39%) and anal mucositis (29%). No grade-3 or higher adverse events were reported. CONCLUSIONS: Adjuvant chemoradiotherapy using capecitabine demonstrated acceptable short-term safety profiles in patients with high-risk submucosal invasive rectal cancer after local resection.