Neoadjuvant chemoimmunotherapy versus chemoradiotherapy for esophageal squamous cell carcinoma: a multicenter cohort study

Purpose The comparative efficacy of neoadjuvant chemoimmunotherapy (NCIT) vs neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (LA-ESCC) remains controversial. Methods and materials This multicenter retrospective cohort study included patients with LA-ESCC who received NCIT or NCRT followed by esophagectomy across 7 Chinese medical centers between January 2012 and January 2024. The primary outcomes were disease-free survival (DFS) and overall survival (OS). Propensity score matching (PSM) was utilized to balance baseline covariates. Results Among 2535 enrolled patients, 1414 received NCIT and 1121 received NCRT. After 1:1 PSM, 1258 patients (629 per group) were evaluated. With a median follow-up of 32.7 months, no significant differences were observed between the NCIT and NCRT groups in DFS (hazard ratio [HR], 1.14; 95% CI, 0.94-1.38; P = .20) or OS (HR, 0.98; 95% CI, 0.77-1.25; P = .89). The 2-year DFS rates were 68.7% (NCIT) vs 72.0% (NCRT), and 2-year OS rates were 81.3% vs 83.7%, respectively. NCIT showed a trend toward improved distant metastasis-free survival (DMFS) (HR, 0.87; 95% CI, 0.69-1.11; P = .27), whereas NCRT was associated with a trend toward improved locoregional recurrence-free survival (LRFS) (HR, 1.22; 95% CI, 0.96-1.56; P = .11). Conclusions NCIT and NCRT demonstrated comparable DFS and OS. These findings suggest that both modalities are valid neoadjuvant strategies, possessing differing strengths in local vs systemic tumor control. These observations await confirmation in prospective trials.