Abstract
BACKGROUND: This study compared the efficacy of neoadjuvant immunochemotherapy (nICT) followed by surgery versus upfront surgery for locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: In this prospective controlled trial (2020-2025), 623 stage II-IIIB ESCC patients were included; 192 received nICT (cisplatin, nab-paclitaxel, sintilimab) before surgery, and 431 underwent direct surgery. Propensity-score matching (PSM) and overlap weighting were used to adjust for baseline confounders. RESULTS: After PSM (144 pairs), the nICT group showed significantly improved progression-free survival (PFS; HR = 0.31, p<0.001) and overall survival (OS; HR = 0.42, p=0.002) compared to the upfront surgery group. The nICT group also had higher 1-/3-year PFS (88.8%/84.3% vs. 68.1%/52.8%) and OS rates (94.8%/84.7% vs. 89.6%/65.2%). Sensitivity analysis using overlap weighting confirmed these robust findings (PFS: HR = 0.37, p<0.001; OS: HR = 0.62, p=0.033). CONCLUSIONS: For locally advanced ESCC, neoadjuvant immunochemotherapy significantly improves both PFS and OS compared to upfront surgery, establishing it as a highly effective treatment strategy.