To evaluate the correlation between clinical complete response (cCR) judged by enhanced computed tomography (CT) and pathological complete response (pCR) after neoadjuvant chemotherapy combined with immunotherapy for esophageal squamous cell carcinoma (ESCC), and analyze its clinical application value in predicting prognosis.

We retrospectively analyzed the clinical data of 266 patients who received neoadjuvant chemotherapy combined with immunotherapy and surgery at The Fourth Hospital of Hebei Medical University from November 2019 to May 2024. Two physicians judged whether cCR was achieved based on enhanced CT images. Then, we analyzed the relationship between cCR and pCR and compared the survival differences of patients.

Among 266 patients, 53 (19.9%) achieved cCR. Among cCR patients, 39 (73.6%) achieved pCR. The sensitivity of cCR for predicting pCR is 50.7% and the specificity is 92.6%. The receiver operating characteristic (ROC) curve demonstrated that cCR had a certain predictive value for pCR [area under the curve (AUC) =0.716, 95% confidence interval (CI) : 0.641–0.792, P<0.001]. Survival curve analysis shows that there is a significant association between pCR and both overall survival (OS; χ²=7.82, P=0.005) and recurrence-free survival (RFS; χ²=6.28, P=0.012). cCR predicted by enhanced CT is also significantly correlated with OS (χ²=5.38, P=0.020) and RFS (χ²=8.39, P=0.004). Multivariate Cox regression analysis revealed that N stage was an independent prognostic factor for both OS and RFS.

Enhanced CT has a certain predictive efficacy for pCR based on cCR in ESCC after neoadjuvant chemotherapy combined with immunotherapy, with low sensitivity and high specificity. It holds certain clinical value in assessing the efficacy of neoadjuvant therapy and predicting prognosis. Multivariate analysis identified N stage as an independent prognostic factor for both OS and RFS.