Prognostic analysis of patients with esophageal squamous cell carcinoma based on tumor differentiation in the setting of neoadjuvant chemotherapy combined with immunotherapy: A single-center retrospective study

BACKGROUND: Neoadjuvant chemotherapy combined with immunotherapy (NACI) has emerged as a promising therapeutic approach for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Tumor differentiation, a key histopathological characteristic, has been well established as a prognostic factor in various malignancies. However, the potential impact of tumor differentiation on treatment outcomes NACI and its association with patient prognosis in the ESCC population remain unclear. METHODS: The clinical data of patients diagnosed with esophageal cancer and treated in the Department of Thoracic Surgery at the Fourth Hospital of Hebei Medical University between November 1, 2019, and November 1, 2022, were retrospectively analyzed. Patients were classified into three groups-G1 (well-differentiated), G2 (moderately differentiated), and G3 (poorly differentiated)-based on pathological examination of specimens. The primary endpoint was overall survival and the identification of risk factors influencing prognosis. RESULTS: The objective response rate (ORR) in the overall population was 63.4%, with a pathological complete response (pCR) rate of 33.5%, which was significantly associated with the poorly differentiated subgroup (P < 0.001). The overall R0 resection rate was 95.7%, with no statistically significant difference observed among the three groups (G3: 91.4%; G2: 97.8%; G1: 100%) (P = 0.724). Furthermore, the 3-year overall survival rate in the poorly differentiated group was 68.4%, The 3-year recurrence-free survival rate in this group was 55.9%. The risk of death (P = 0.011) and recurrence (P < 0.001) are significantly different from the other two groups of people, a finding supported by regression analysis. Even if the poorly differentiated population reaches pCR, their prognosis is still poor, but pathological lymph node status remains the main prognostic stratification factor, Both lymph node metastasis and poor tumor differentiation emerged as strong independent risk factors of overall survival (OS) and disease-free survival (DFS). CONCLUSIONS: Patients with poorly differentiated tumors may achieve excellent short-term outcomes, yet they have the poorest long-term prognosis. Lymph node metastasis and poor tumor differentiation are strong prognostic factors.