Impact of long-course neoadjuvant radiation on postoperative low anterior resection syndrome and stoma status in rectal cancer: long-term functional follow-up of a randomized clinical trial

BACKGROUND: Neoadjuvant radiation has been increasingly associated with postoperative bowel dysfunction, including low anterior resection syndrome (LARS). Although permanent stoma often results from severe bowel dysfunction and significantly impacts quality of life, the presence of stoma paradoxically excludes patients from functional follow-up. Hence, stoma status is rarely reported along with LARS, while assessment of both is essential for the comprehensive evaluation of bowel dysfunction in long-term survivors of rectal cancer. METHOD: Patients enrolled into the Neoadjuvant FOLFOX6 Chemotherapy with or without Radiation in Rectal Cancer (FOWARC) multicentre randomized clinical trial were randomized to receive long-course neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by sphincter-saving proctectomy and longitudinal follow-up. The primary outcome of the trial was disease-free survival. LARS score and stoma status were assessed secondarily for postoperative bowel function in the largest single-centre cohort of the trial. RESULTS: Overall, 327 patients with locally advanced rectal cancer were enrolled in the original trial and 203 responded after a median follow-up of 83.4 months, of whom 24 (11.8 per cent) had persistent stoma, and 48 patients (23.6 per cent) reported major LARS. Compared with the nCT group, the nCRT group reported more persistent stomas (16.5 per cent versus 4.9 per cent, P = 0.014), and more major LARS in patients without persistent stoma (34.7 per cent versus 16.7 per cent, P = 0.003). The combined prevalence of persistent stoma and major LARS was significantly higher in the nCRT group (45.5 per cent versus 20.7 per cent, P < 0.001). Long-course neoadjuvant radiation (OR 2.20, 95 per cent c.i. 1.10 to 4.40, P = 0.027), height of anastomosis (OR 0.74, 95 per cent c.i. 0.61 to 0.91, P = 0.004), and anastomotic leak (OR 4.97, 95 per cent c.i. 2.24 to 11.05, P < 0.001) were associated with persistent stoma and major LARS in multivariate analysis. CONCLUSION: More than one-third of patients receiving sphincter-saving proctectomy reported major LARS or persistent stoma at long-term follow-up. Long-course neoadjuvant radiation, low anastomosis, and postoperative leak are independent risk factors for persistent stoma and major LARS.