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

Dis Colon Rectum. 2016 Oct;59(10):934-42. doi: 10.1097/DCR.0000000000000665.

Abstract

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.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Anastomosis, Surgical / adverse effects
  • Anastomosis, Surgical / methods
  • Anastomotic Leak* / etiology
  • Anastomotic Leak* / prevention & control
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Chemoradiotherapy / adverse effects*
  • Chemoradiotherapy / methods
  • Chemotherapy, Adjuvant / adverse effects*
  • Chemotherapy, Adjuvant / methods
  • Colectomy / methods
  • Constriction, Pathologic / diagnosis
  • Constriction, Pathologic / etiology
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / adverse effects
  • Humans
  • Male
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • Organoplatinum Compounds / adverse effects
  • Outcome and Process Assessment, Health Care
  • Oxaliplatin
  • Preoperative Care* / adverse effects
  • Preoperative Care* / methods
  • Proctitis* / diagnosis
  • Proctitis* / etiology
  • Radiation Dosage
  • Radiation Injuries / diagnosis*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / radiotherapy*
  • Rectal Neoplasms / surgery

Substances

  • Antineoplastic Agents
  • Organoplatinum Compounds
  • Oxaliplatin
  • Fluorouracil

Associated data

  • ClinicalTrials.gov/NCT01211210