Neoadjuvant chemotherapy improves overall survival in stage III but not in stage II colon cancer: A propensity score–matched analysis of the National Cancer Database

Background: Neoadjuvant chemotherapy has been recently suggested for advanced colon cancer, but little is known about the impact on short-term outcomes and overall survival. In this study, we aimed to evaluate the effect of neoadjuvant chemotherapy on survival in stage II-III colonic adenocarcinoma. Methods: A retrospective analysis of the colon cancer US National Cancer Database from 2006 to 2019 was performed. Patients treated with neoadjuvant chemotherapy were matched using propensity score to controls (ratio 1:1). The primary outcome was 5-year overall survival. Results: In total, 1,275 patients (1.3%) with clinical stage II-III colonic adenocarcinoma received neoadjuvant chemotherapy. After matching, the neoadjuvant chemotherapy group included 783 patients. The restricted mean 5-year overall survival in the neoadjuvant chemotherapy group was significantly higher compared with controls (48.9 vs 44.9 months, P = .003). Stratified by disease stage, neoadjuvant chemotherapy was associated with a significantly longer overall survival (47.5 vs 41.2 months; P = .001) in stage III while showing an equivalent overall survival in stage II (50.3 vs 48.6 months; P = .2). The benefit in overall survival was pronounced in stage T4 and positive nodal disease. Cox regression analysis in patients with stage III revealed that neoadjuvant chemotherapy was associated with a 21% reduction in mortality risk (hazard ratio, 0.79; 95% confidence interval, 0.65–0.96; P = .01). Neoadjuvant chemotherapy was associated with lower rates of 30-day readmission (3.5% vs 7.4%, P = .001), 30-day mortality (0.9% vs 3.8%, P < .001), and 90-day mortality (2.9% vs 8.5%, P < .001). Conclusion: Preoperative neoadjuvant chemotherapy is associated with improved overall survival in patients with stage III colon cancer, mainly in patients with T4 disease.