Neoadjuvant chemoimmunotherapy versus chemotherapy for locally advanced esophageal squamous cell carcinoma: a retrospective cohort study

BACKGROUND: Neoadjuvant chemoimmunotherapy (NCIT) has shown promising activity in locally advanced esophageal squamous cell carcinoma (ESCC), but comparative evidence against neoadjuvant chemotherapy (NCT) alone remains limited. This study aimed to compare the pathological response and perioperative safety of NCIT versus NCT in patients with locally advanced ESCC. METHODS: This single-center retrospective cohort study included 199 patients with locally advanced ESCC who underwent neoadjuvant therapy followed by esophagectomy between 2017 and 2023. Among them, 131 patients received NCIT and 68 received NCT alone. Pathological response was assessed using major pathological response (MPR), pathological complete response (pCR), and tumor regression grade (TRG). Treatment-related adverse events (TRAEs) and postoperative outcomes, including 30-day and 90-day mortality, were evaluated. To reduce confounding from baseline imbalance, 1:1 propensity score matching (PSM) was performed as the primary adjusted analysis. RESULTS: In the overall cohort, MPR was achieved in 51 of 131 patients in the NCIT group and 17 of 68 patients in the NCT group (38.93% vs. 25.00%; absolute risk difference [ARD], + 13.93%; 95% CI, + 0.02% to + 26.18%; odds ratio [OR], 1.91; 95% CI, 1.00-3.67; P = 0.049). The distribution of TRG also favored NCIT (P = 0.015). After 1:1 propensity score matching, 67 matched pairs were analyzed, and the NCIT group continued to show a higher MPR rate than the NCT group (44.78% vs. 25.37%; ARD, + 19.40%; 95% CI, + 3.24% to + 34.23%; OR, 2.39; 95% CI, 1.15-4.96; P = 0.019). The pCR rate was numerically higher in the NCIT group but did not reach statistical significance. Treatment-related adverse events were comparable between the two groups (80.2% vs. 83.8%; P = 0.528). No deaths occurred within 30 days, whereas one death occurred within 90 days in each group. CONCLUSION: NCIT was associated with improved major pathological response compared with NCT alone in patients with locally advanced ESCC, while maintaining comparable treatment-related toxicity and short-term postoperative safety. These findings support NCIT as a promising neoadjuvant strategy for locally advanced ESCC and provide a rationale for further prospective validation.