Early tumor shrinkage and depth of response during treatment with immune checkpoint inhibitors as predictors of overall survival in patients receiving second-line or later therapy for advanced esophageal squamous cell carcinoma: a retrospective study

Early tumor shrinkage (ETS) and depth of response (DoR) reflect tumor response heterogeneity and may predict immunotherapy outcomes. This study evaluated the prognostic values of ETS and DoR in patients with advanced esophageal squamous cell carcinoma (ESCC) who received second-line or later immune checkpoint inhibitor (ICI) therapy. We retrospectively analyzed 121 patients with advanced/metastatic ESCC who received ICI therapy after treatment failure. ETS (at 8 weeks) and DoR (maximal shrinkage) were assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Associations with overall survival (OS) were evaluated using Kaplan–Meier and Cox regression analyses. Longer OS was significantly associated with achieving ETS ≥ 10% ( p < 0.05) and DoR ≥ 13% ( p < 0.05), as well as with the absence of lymphatic metastasis ( p < 0.05). In multivariate analysis, DoR ≥ 13% (hazard ratio [HR] = 2.44; 95% confidence interval [CI] 1.32–4.52; p = 0.005) and lymphatic metastasis (HR = 0.49; 95% CI 0.27–0.89; p = 0.020) were independent prognostic factors for OS. Notably, patients who achieved both high ETS and deep DoR (optimal responders) had the most favorable survival outcomes, whereas those achieving neither had the poorest survival (log-rank p < 0.001), demonstrating that ETS and DoR provide complementary prognostic information. DoR is an independent determinant of survival in patients with advanced ESCC treated with later-line ICIs. Early tumor shrinkage provides synergistic prognostic information. Their combined assessment offers a refined stratification tool to guide clinical decision-making. This study was approved by the Institutional Review Board of the First Affiliated Hospital of Zhengzhou University (No. 2025-KY-0988-002). All patients signed an informed consent form before the examination.