Real-world comparative effectiveness of neoadjuvant chemoimmunotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma: a retrospective cohort study

Background: Neoadjuvant chemoimmunotherapy (NCIT) has shown higher pathologic response rates than neoadjuvant chemotherapy (NCT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC). Recent studies have reported comparative survival outcomes, but evidence from extended follow-up remains limited. Methods: This retrospective cohort study was conducted at a large cancer center in southern China. Consecutive LA-ESCC patients who underwent esophagectomy following NCT or NCIT from April 2012 to February 2023 were included. Pathological outcomes, disease-free survival (DFS), and overall survival (OS) were compared between the NCT and NCIT groups before and after applying stabilized inverse probability of treatment weighting (IPTW). Results: The study included 478 patients (NCT group, n = 230; NCIT group, n = 248). The median follow-up was 45.6 months. After IPTW adjustment, the NCIT group exhibited significantly higher pathological complete response rates than the NCT group (29.8% vs. 9.5%, P < 0.001). Patients receiving NCIT experienced significantly longer OS [hazard ratio (HR) = 0.37; 95% confidence interval (CI), 0.25–0.54; P < 0.001] and DFS (HR = 0.49; 95% CI, 0.36–0.68; P < 0.001) compared with those receiving NCT. The 3-year OS rates were 81.8% in the NCIT group versus 57.7% in the NCT group, while the 3-year DFS rates were 69.3% and 47.9%, respectively. Additionally, the NCIT group had lower 2-year observed proportions of overall recurrence (11.3% vs. 30.6%), locoregional recurrence (2.6% vs. 8.7%), and distant metastasis (1.5% vs. 8.7%). Conclusions: Compared with NCT, NCIT was associated with improved survival in patients with LA-ESCC. These findings support NCIT as a promising neoadjuvant option, although prospective validation remains necessary.