Efficacy and Safety of Neoadjuvant Immunotherapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma: A Network Meta-Analysis and Real-World Study

Mengfei Sun¹Pengjie Yang²Ling Qi³Ting Yang¹Weishi Wang⁴Yongjun Yu⁵Jingjing ZHANG¹Benben Zhu^2*Yong Li^6*

• ¹Inner Mongolia Medical University, Hohhot, China
• ²Peking University Cancer Hospital Inner Mongolia Hospital, Hohhot, China
• ³Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
• ⁴The Affiliated Hospital of Southwest Medical University, Luzhou, China
• ⁵The Second Hospital of Chifeng, Chifeng, China
• ⁶Department of Thoracic Surgery, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Introduction: This study aimed to explore the efficacy and safety of neoadjuvant immunotherapy combination regimens in locally advanced resectable esophageal squamous cell carcinoma (ESCC), and evaluate the pros and cons of different regimens and their impacts on survival by integrating network meta-analysis (NMA) and real world studies (RWS). ESCC accounts for approximately 90% of global esophageal cancer cases, with over half occurring in China. Although neoadjuvant chemoradiotherapy improves prognosis, unmet clinical needs persist; the optimal neoadjuvant immunotherapy regimen remains controversial. Current large-scale randomised controlled trials (RCTs) suffer from limited sample sizes and fail to adequately reflect the treatment realities of patients in the Chinese real-world setting. Methods: Systematic searches of databases including PubMed, Embase, Web of Science, and CNKI identified eligible RCTs and cohort studies for NMA. Concurrently, clinical data of 113 such ESCC patients who received neoadjuvant immunotherapy combination treatment followed by surgery at National Cancer Centre of China (January 2021–December 2023) were retrospectively collected, with logistic and Cox regression analyses used to assess associations between factors (e.g., MPR, radiotherapy) and survival. Result: NMA results showed Sintilimab plus chemoradiotherapy had the highest pathological complete response (pCR) rate, Camrelizumab plus nab-paclitaxel/platinum performed best in major pathological response (MPR) and radical resection with negative surgical margins (R0 resection) rates, and Sintilimab plus nab-paclitaxel/platinum had the lowest adverse event (AE) incidence. Real-world data revealed a significantly higher MPR rate in the Camrelizumab group than the Tislelizumab group (46.9% vs 12.5%, P=0.0213). Multivariate analysis indicated MPR and primary tumor T response were independent protective factors for overall survival (OS) and progression-free survival (PFS), while neoadjuvant radiotherapy correlated with poorer OS and PFS. Conclusion: Neoadjuvant immunotherapy combinations (notably Cam+nab-TP) exhibit favorable efficacy in this ESCC subtype, and MPR serves as a reliable surrogate endpoint for long-term survival. The survival benefit of radiotherapy requires careful assessment, and clinical decisions should balance efficacy and safety, as these findings provide evidence for individualized treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251174359.