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

Jpn J Clin Oncol. 2021 Apr 30;51(5):707-712. doi: 10.1093/jjco/hyaa260.


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/m2 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.

Keywords: adjuvant chemoradiotherapy; capecitabine; local resection; rectal cancer.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Chemoradiotherapy, Adjuvant / adverse effects
  • Chemoradiotherapy, Adjuvant / methods*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Quality of Life
  • Rectal Neoplasms / drug therapy*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery*
  • Young Adult