Clinical Outcomes of Neoadjuvant Chemoimmunotherapy Versus Chemoradiation Combined with Immunotherapy in Locally Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis

Neoadjuvant chemoimmunotherapy (NCIT) has emerged as a promising strategy for patients with esophageal squamous cell carcinoma (ESCC). However, whether neoadjuvant chemoradiation-immunotherapy (NCRI) can further improve therapeutic efficacy remains uncertain.

This study prospectively enrolled and retrospectively analyzed 557 consecutive patients with locally advanced ESCC who underwent neoadjuvant therapy between December 2019 and January 2025. The participants were stratified into two treatment cohorts: those receiving NCIT and those undergoing NCRI. To mitigate potential selection bias and ensure balanced baseline characteristics between groups, a 1:1 propensity score-matching (PSM) protocol was implemented incorporating multiple clinically relevant covariates to assess short-term pathologic outcomes and long-term survival.

After PSM, these baseline characteristics were well balanced, with 124 patients in each group. The NCRI group demonstrated superior pathologic outcomes, with a significantly higher pathologic complete response (pCR) rate (41.1% vs 19.4%; P < 0.001) and a lower tumor regression score (TRS; P < 0.001), but also a higher incidence of postoperative pulmonary complications (37.1% vs 16.9%; P < 0.001). Despite these differences, no significant variation in overall survival (OS; P = 0.837) or disease-free survival (DFS; P = 0.429) was observed between the two groups during the follow-up period.

The addition of radiotherapy to NCIT significantly improved pCR rates compared with NCIT alone, but was associated with a higher incidence of postoperative pulmonary complications. However, this pathologic benefit did not translate into superior long-term survival outcomes in either OS or DFS.