Impact of Long-Course Neoadjuvant Radiation on Postoperative Low Anterior Resection Syndrome and Quality of Life in Rectal Cancer: Post Hoc Analysis of a Randomized Controlled Trial

Neoadjuvant radiation is recommended for locally advanced rectal cancer, with proven benefit in local control but not in disease-free survival. However, the impact of long-course radiation on postoperative bowel function and quality of life (QOL) remains controversial. This study aimed to investigate the impact of long-course neoadjuvant radiation on bowel function and QOL, and to identify risk factors for severe bowel dysfunction. Patients who underwent long-course neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by radical low anterior resection for locally advanced rectal cancer were recruited from the FOWARC randomized controlled trial. Low anterior resection syndrome (LARS) score and European Organisation for Research and Treatment of Cancer (EORTC) C30/CR29 questionnaires were used to assess bowel function and QOL, respectively. Overall, 220 patients responded after a median follow-up of 40.2 months, of whom 119 (54.1%) reported major LARS, 74 (33.6%) reported minor LARS, and 27 (12.3%) reported no LARS. Compared with the nCT group, the nCRT group reported more major LARS (64.4% vs. 38.6%, p < 0.001) and worse QOL. Long-course neoadjuvant radiation (OR 2.20, 95% CI 1.24–3.91; p = 0.007), height of anastomosis (OR 0.74, 95% CI 0.63–0.88; p < 0.001), and diverting ileostomy (OR 2.59, 95% CI 1.27–5.30; p = 0.009) were independent risk factors for major LARS. Long-course neoadjuvant radiation, along with low anastomosis, are likely independent risk factors for postoperative bowel function and QOL. Our findings might have implications for alleviating LARS and improving QOL by informing selection of neoadjuvant treatment.