Preoperative Treatment for Potential Resectable Esophageal Cancer: Insights from a Nationwide Real-World Study

Jie Tang¹HUI LIN²Chengli Du¹Jingrong Yang³Chenwei Li⁴Yong Lin⁵Shaogeng Chen⁶Zhijun Huang⁷Haitao Wang⁸Jun-Hui Fu⁹Zhengliang Tu^1*

• ¹First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China
• ²Fujian Provincial Cancer Hospital, Fuzhou, China
• ³900th Hospital of the People's Liberation Army Joint Logistic Support Force, Fuzhou, China
• ⁴The First Affiliated Hospital of Ningbo University, Ningbo, China
• ⁵Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou, China
• ⁶Fujian Medical University Affiliated First Quanzhou Hospital, Quanzhou, China
• ⁷Second Affiliated Hospital of Fujian Medical University, Quanzhou, China
• ⁸Zhejiang Provincial People's Hospital, Hangzhou, China
• ⁹Shantou Central Hospital, Shantou, China

Background This nationwide real-world study evaluates the efficacy and safety of serplulimab-based neoadjuvant therapy in esophageal cancer, addressing the clinical feasibility and outcomes of this emerging approach. Methods A retrospective analysis was conducted across 9 institutions in China, including 95 esophageal cancer patients who received serplulimab-based neoadjuvant chemoimmunotherapy followed by radical surgery. Pathologic complete response (pCR), major pathologic response (MPR), tumor response, and adverse events (AEs) were analyzed. Subgroup analyses explored the impact of PD-L1 expression and other clinical factors on treatment outcomes. Results The pCR rate was 23.16%, and the MPR rate was 41.05%. Tumor and nodal downstaging rates were 56.84% and 61.05%, respectively. Logistic regression showed that PD-L1-positive patients had higher odds of achieving pCR and MPR; however, due to the small number of pCR events and wide confidence intervals, these findings should be interpreted with caution. The overall AE incidence was 96.84%, with 28.42% experiencing Grade ≥3 AEs. No new safety signals were identified, and patients generally tolerated the treatment well. Conclusion This study highlights the potential of serplulimab-based neoadjuvant therapy in transforming unresectable esophageal tumors into resectable disease with manageable toxicity. However, only patients who completed surgery were included, which may introduce potential bias. While these findings support its clinical feasibility, the short follow-up period limits survival interpretation, and larger prospective trials are needed to validate its efficacy and explore biomarker-based strategies.