Preliminary Surgical Outcomes From Multicenter, Randomized Phase Iii Trial (Science): Impact of Neoadjuvant Sintilimab-Based Regimens on Resectable Locally Advanced Escc

Background While neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT) followed by surgery is standard for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC), the integration of immune checkpoint inhibitors like Sintilimab remains investigational. This trial evaluated the short-term surgical outcomes of three neoadjuvant approaches: Sintilimab combined with nCT, Sintilimab with nCRT, and nCRT alone. Methods Eligible patients (N = 146) with LA-ESCC (cT1N2–3 M0 or cT2–4aN0-3 M0) were randomized 1:1:1 to Group A (Sintilimab + nab-paclitaxel/carboplatin, 2 cycles), Group B (Sintilimab + nCRT [41.4 Gy]), or Group C (nCRT alone). Surgery was performed 4–8 weeks post-neoadjuvant therapy. Primary surgical endpoints included R0 resection rate, pathological complete response (pCR) rate, and postoperative complications; other endpoints encompassed treatment-emergent adverse events (TEAEs) and perioperative mortality. Results All 146 patients completed neoadjuvant therapy and underwent surgery, with a 100% R0 resection rate across all groups. Group A had a MIE of 97.8%, with the majority of Thoracoscopic (50.0%) and Robotic (47.8%). Group C demonstrated a similar rate of 98.2%, with 63.6% of patients receiving Thoracoscopic and 34.5% undergoing Robotic Assisted McKeown. The pCR rates differed significantly among groups, with Group A achieving a pCR rate of 13%, Group B 60%, and Group C 47.3%. Postoperative complications were significantly higher in Group A (71.7%) compared to Group B (46.7%) and Group C (49.1%) (P < 0.001), with no perioperative mortality. Conclusion The addition of Sintilimab to nCRT (Group B) achieved superior pathological response without compromising surgical safety, as evidenced by a high R0 rate and lower complication rates compared to Sintilimab + nCT (Group A). While nCRT-based regimens (Groups B/C) had higher Grade ≥ 3 TEAEs, these did not translate to increased surgical risk. These results support the feasibility of Sintilimab-enhanced nCRT as a neoadjuvant strategy for LA-ESCC, warranting further evaluation of long-term survival benefits. Clinical Trial Information: NCT05244798.