Neoadjuvant Chemoimmunotherapy Versus Chemotherapy Plus Esophagectomy for Esophageal Squamous Cell Carcinoma: Primary Result of a Randomized Clinical Trial

Abstract Background Neoadjuvant therapy is necessary for patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, the optimal regimen of neoadjuvant therapy is still under debate. The aim of this trial was to evaluate the value of chemoimmunotherapy as neoadjuvant regimen, comparing with chemotherapy. Methods A prospective trial was conducted in Fudan University Shanghai Cancer Center. Patient with locally advanced ESCC (T2–4aN0-3 M0) were randomized to receive chemoimmunotherapy (sintilimab, nab-paclitaxel, cisplatin) or chemotherapy (nab-paclitaxel, cisplatin). Esophagectomy was performed within 4–6 weeks after treatment. The primary outcome was 1-year event-free survival. Results Between December 5th 2023 and May 15th 2025, a total of 177 patients has been included, of which 87 received immunotherapy and 90 received chemotherapy. Majority of treatment-related adverse events were minor. Of the 121 patients who had surgery by May 15th, 2025, 55 (45.5%) had ivor-lewis procedure and 66 (54.5%) MecKowen procedure. Pathological complete response (pCR) was observed in 7 patients (11.7%) in the immunochemotherapy arm, and 1 (1.6%) in the chemotherapy arm, whereas major pathological response (mPR, less than 10% residual tumor) was 33 (55.0%) in the immunochemotherapy arm and 26 (42.6%) in the chemotherapy arm. Conclusion Both immunochemotherapy and chemotherapy were safe as neoadjuvant treatment regimen. More patients had pCR and mPR after immunochemotherapy. Long-term follow-up in the future could clarify the value of immunotherapy regarding the survival benefit.