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

Abstract

Background: Neoadjuvant chemotherapy alone (with radiation omission) for locally advanced rectal cancer has been evaluated in several randomized controlled trials. Although 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 therapy 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 nonreversal, 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 noninferior to chemoradiation therapy. Anastomotic leak and use of diverting ostomy were reported in 3 of the 4 trials, whereas 30-day postoperative morbidity and ostomy nonreversal were reported in only 2 trials. Bowel function was measured in 3 trials but was measured and reported differently in each trial. On meta-analysis, neoadjuvant chemotherapy was associated with a significant reduction in anastomotic leak (relative risk [RR] 0.54; 95% CI, 0.35-0.81), use of diverting ostomy (RR 0.79; 95% CI, 0.70-0.88), and ostomy nonreversal (RR 0.37; 95% CI, 0.15-0.93). There was no association between neoadjuvant chemotherapy and 30-day postoperative morbidity (RR 0.88; 95% CI, 0.53-1.45).

Limitations: A small number of included trials with heterogeneity in outcome definitions was the limitation.

Conclusions: Important surgical outcomes were not reported in trials comparing neoadjuvant chemotherapy alone to chemoradiation therapy 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 nonreversal. See Video Abstract .

Keywords: Chemotherapy; Neoadjuvant therapy; Radiation omission; Rectal cancer; Surgical outcomes.