Impacts of Mitochondrial Status After Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma Patients

The prognostic significance of mitochondrial status after neoadjuvant chemotherapy (NAC) and its association with the tumor microenvironment (TME) in esophageal squamous cell carcinoma (ESCC) remains unclear. We analyzed 202 ESCC patients who underwent NAC followed by surgical resection. Mitochondrial status was quantified using an objective, immunohistochemistry-based scoring system (Mito-score). The optimal cut-off value was determined by receiver operating characteristic curve analysis. Clinicopathological features, TME parameters (T-cell density and programmed death ligand-1 [PD-L1] expression), and survival outcomes were compared between high and low Mito-score groups. Multivariate Cox regression identified independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). The high and low Mito-score groups comprised 140 (69.3%) and 62 (30.7%) patients, respectively. NAC response rates and ypStages III-IV frequencies were similar in the two groups. PD-L1 expression was significantly higher in high Mito-score tumors (p = 0.04), while T-cell densities did not differ. High Mito-score was associated with significantly worse OS (3-year OS: 51.9% vs. 72.6%, p = 0.001) across both ypStages I-II (p = 0.047) and ypStages III-IV (p = 0.01) subgroups. In ypStages III-IV, high Mito-score was also linked to poorer CSS (p = 0.01). Multivariate analysis confirmed high Mito-score to be an independent predictor of unfavorable OS and CSS. Overall, high Mito-score after NAC identifies ESCC patients with significantly poorer survival, particularly among those with advanced pathological stages, thereby possibly serving as an independent prognostic biomarker.