Neoadjuvant Chemotherapy Without Radiation for Locally Advanced Rectal Cancer: A Meta-analysis of Surgical Outcomes after Total Mesorectal Excision

BACKGROUND: Neoadjuvant chemotherapy alone (with radiation omission) for locally advanced rectal cancer has been evaluated in several randomized controlled trials. While oncologic outcomes have been well described, the impact of this treatment strategy on surgical outcomes is unknown. OBJECTIVE: To evaluate how important surgical outcomes were reported in previous trials comparing neoadjuvant chemotherapy to chemoradiation for locally advanced rectal cancer and to perform a meta-analysis of available data. DATA SOURCES: A systematic review was conducted using MEDLINE, Embase, and the Cochrane Library Databases. STUDY SELECTION: All published randomized controlled trials that compared neoadjuvant chemotherapy to chemoradiation for MRI-staged rectal adenocarcinoma. INTERVENTIONS: Neoadjuvant chemotherapy alone (with radiation omission). MAIN OUTCOME MEASURES: Postoperative surgical outcomes, including anastomotic leak, diverting ostomy use, ostomy non-reversal, 30-day postoperative morbidity, and postoperative bowel function. RESULTS: Four randomized controlled trials met eligibility criteria and were included for data analysis. Oncologic outcomes demonstrated that neoadjuvant chemotherapy was equivalent or non-inferior to chemoradiation. Anastomotic leak and use of diverting ostomy were reported in 3 of 4 trials while 30-day postoperative morbidity and ostomy non-reversal were only reported in 2 of 4 trials. Bowel function was measured in 3 of 4 trials but was measured and/or reported differently in each trial. On meta-analysis, neoadjuvant chemotherapy was associated with a significant reduction in anastomotic leak (RR: 0.54, 95% 0.35-0.81), use of diverting ostomy (RR: 0.79, 95% 0.70-0.88), and ostomy non-reversal (RR: 0.37, 95% 0.15-0.93). There was no association between neoadjuvant chemotherapy and 30-day postoperative morbidity (RR: 0.88, 0.53-1.45). LIMITATIONS: Small number of included trials with heterogeneity in outcome definitions. CONCLUSIONS: Important surgical outcomes were not reported in trials comparing neoadjuvant chemotherapy alone to chemoradiation for locally advanced rectal cancer. Based on the limited data available, chemotherapy alone was associated with reduced risk of anastomotic leak, diverting ostomy use, and ostomy non-reversal. See Video Abstract .