Evaluation of the efficacy and safety of different cycles of neoadjuvant chemotherapy combined with immunotherapy in locally advanced esophageal squamous cell carcinoma: a multi-center, real-world study

Neoadjuvant chemotherapy combined with immunotherapy (nCIT) can improve radiologic and pathological responses in resectable, locally advanced esophageal squamous cell carcinoma (ESCC), yet the optimal number of preoperative cycles is unknown. We conducted a multicenter, real-world retrospective study of 284 patients with resectable ESCC treated between 2019 and 2024 who underwent radical esophagectomy after 1–4 cycles of nCIT. Patients were grouped as 1–2 versus 3–4 cycles and were additionally balanced using 1:1 propensity score matching. The primary endpoint was recurrence-free survival (RFS); secondary endpoints included objective response rate (ORR), pCR, adverse events (AEs), and postoperative complications. Before matching, ORR and pCR were higher with 3–4 cycles than with 1–2 cycles (ORR 85.6% vs. 75.1%; pCR 35% vs. 21%). After matching, these differences were not statistically significant (ORR 84.7% vs. 74.0%; pCR 31% vs. 22%). Median RFS was not reached in either group, and RFS rates were comparable after matching. The incidence and severity of AEs and postoperative complications were similar between groups, with leukopenia and pneumonia being most frequent, and no increase in severe toxicity with additional cycles. Subgroup analyses suggested potential heterogeneity of effect, with limited signals of benefit in earlier clinical stage and possible unfavorable outcomes in patients with nodal disease. Overall, 1–2 and 3–4 cycles of nCIT showed similar matched outcomes and safety.