Abstract
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) remains a significant global health burden. Neoadjuvant therapy followed by surgery is the standard treatment for locally advanced ESCC, yet optimal strategies to enhance efficacy and reduce recurrence are still being explored. This study aimed to compare the real-world safety and efficacy of neoadjuvant immunochemotherapy (nICT) versus neoadjuvant chemotherapy (nCT) in patients with locally advanced ESCC. METHODS: We retrospectively reviewed 164 patients with stage II-IVA ESCC who received either nICT (n = 118) or nCT (n = 46) followed by radical esophagectomy at Tongji Hospital between January 2019 and April 2024. Clinical characteristics, treatment-related adverse events (TRAEs), radiological and pathological responses, postoperative complications, and survival outcomes were analyzed. Kaplan-Meier analysis and Cox regression models were used to evaluate disease-free survival (DFS) and overall survival (OS). RESULTS: The overall incidence of TRAEs was comparable between the nICT and nCT groups (87.3% vs. 86.9%, p > 0.05), with no treatment-related deaths. The nICT group demonstrated significantly higher rates of pathological complete response (pCR: 27.1% vs. 13.0%, p < 0.05) and major pathological response (MPR: 49.2% vs. 30.4%, p < 0.05) compared to the nCT group. Postoperative complication rates were similar across groups. At a median follow-up of 25.5 months, the nICT group showed superior DFS (HR = 1.696, 95% CI: 1.043-2.758, p = 0.016), while OS did not differ significantly (p = 0.064). CONCLUSIONS: NICT is a safe and effective approach for locally advanced ESCC, offering improved pathological response and DFS compared to chemotherapy alone. These findings support the integration of immunotherapy into neoadjuvant regimens for ESCC.