Impact of Preoperative Radiotherapy on Anastomotic Leakage and Stenosis After Rectal Cancer Resection: Post Hoc Analysis of a Randomized Controlled Trial

BACKGROUND: Evidence regarding the effect of preoperative radiotherapy on anastomotic integrity remains conflicting in rectal cancer surgery. Prospective comparisons with appropriate controls are needed. OBJECTIVE: This study aimed to assess the impact of preoperative radiotherapy on anastomotic leakage and stenosis after rectal cancer resection. DESIGN: This was a post hoc analysis of a randomized controlled trial (NCT01211210). SETTINGS: Data were retrieved from the leading center of the trial, which is a tertiary hospital. PATIENTS: The full analysis population of 318 patients was included. INTERVENTIONS: Patients were randomly assigned to receive preoperative radiation (50 Gy per 25 fractions) and 5-fluorouracil infusion, alone (arm A) or combined with oxaliplatin (arm B), or preoperative chemotherapy with 5-fluorouracil and oxaliplatin without radiation (arm C). MAIN OUTCOME MEASURES: The rates of anastomotic leakage and stenosis were calculated for each treatment arm. Multivariate analysis was used to verify the effect of preoperative radiotherapy. RESULTS: The treatment arms were comparable in terms of most baseline characteristics, but more diversions were used in the chemoradiotherapy arms. Anastomotic leakage occurred in 20.2% of patients in arm A, 23.6% of patients in arm B, and 8.5% of patients in arm C (p = 0.007). The corresponding rates of stenosis were 17.0%, 18.9%, and 6.8% (p = 0.02). Multivariate analysis confirmed the correlation between preoperative radiotherapy and clinical leakage (p = 0.02), which was associated with delayed stenosis (p < 0.001). For patients undergoing chemoradiotherapy, radiation proctitis was identified as an independent risk factor for clinical leakage (p = 0.01) and stenosis (p < 0.001). LIMITATIONS: The main limitations were discrepancies in stoma creation and chemotherapy regimen among the treatment arms. CONCLUSIONS: Preoperative radiotherapy increases the risk of anastomotic leakage and stenosis after rectal cancer resection. Clinical leakage independently contributes to the development of stenosis.