Adjuvant immunotherapy versus observation in patients with lymph node-positive status after neoadjuvant chemotherapy for esophageal squamous cell carcinoma: a prospective, single-center, controlled phase II study

Background: For locally advanced esophageal squamous cell carcinoma (ESCC), patients with lymph node-positive status after neoadjuvant chemotherapy (NCT) combined with surgery often experience a high recurrence rate and poor prognosis. Currently, there is no recommended adjuvant treatment. Materials and methods: We conducted a prospective, single-center, controlled clinical trial to evaluate the value of checkpoint inhibitors as adjuvant treatment for lymph node-positive patients with ESCC after NCT. Clinical stage II to IVa ESCC patients who received NCT and R0 resection with lymph node-positive status were enrolled and allocated to receive Toripalimab or be part of the observation group at a 1:1 ratio. The trial intervention period lasted up to 1 year. The primary endpoint of the study was disease-free survival (DFS). Results: The median follow-up time for all patients was 50 months (the last follow-up time was in April 2025). The 1- and 3-year DFS rates were 75.0% vs. 46.2% and 59.4% vs. 38.5% ( P = 0.028) in the immunotherapy group and the observation group, respectively; the corresponding overall survival rates were 92.9% vs. 80.8% and 66.6% vs. 42.0% ( P = 0.011). The mean duration of Toripalimab intervention in the immunotherapy group was 6 months (0.7–12.0 months). The incidence of any-grade treatment-related adverse events (TRAEs) in the immunotherapy group was 71.4%, which was higher than the 46.2% in the observation group, but the difference was not statistically significant ( P = 0.059). TRAEs were mainly grade 1–2, and the proportion of grade ≥3 TRAEs was 25.0% and 11.5% ( P = 0.298) in the two groups, respectively; no patients in either group died due to adverse reactions. Conclusion: For patients with locally advanced ESCC who are lymph node-positive after NCT, adjuvant immunotherapy can improve survival compared to clinical observation. This study provides some evidence for adjuvant immunotherapy in these high-risk patients.