A pathologic classification approach in esophageal squamous cell carcinoma following neoadjuvant immunochemotherapy: Distinguishing postoperative outcomes and exploring the potential benefit of adjuvant therapy.

Abstract

Neoadjuvant immunochemotherapy has demonstrated promising efficacy in locally advanced esophageal squamous cell carcinoma (ESCC), yet the role of adjuvant therapy remains unclear. This study aimed to develop a pathologic classification scheme to distinguish postoperative outcomes and explore the potential benefit of adjuvant therapy. This study retrospectively collected data on patients with locally advanced ESCC who underwent radical esophagectomy after neoadjuvant immunochemotherapy between 2019 and 2022. The primary outcome was recurrence-free survival (RFS), and secondary outcomes included recurrence patterns, overall survival, locoregional recurrence-free survival, and distant metastasis-free survival. The Kaplan-Meier method was used to plot survival curves, propensity score matching was used to match different groups, and Cox proportional hazards models identified factors affecting prognosis. Among 333 eligible patients, the overall pathologic complete response (pCR) rate was 25.8%. With a median follow-up of 23.8 months, the 1-year and 2-year RFS rates were 77.0% and 63.2%, respectively. Multivariable analysis identified ypN as the primary factor influencing RFS, while both ypN and MPR status were key determinants of recurrence patterns. A classification approach based on MPR and ypN status was developed to distinguish patient subgroups with different RFS and recurrence patterns. Patients with ypN0 had a favorable prognosis. In ypN⁺ patients, MPR was linked to more locoregional recurrences, while non-MPR cases showed mainly distant metastases. Among MPR ypN⁺ patients, adjuvant therapy was associated with improved RFS (hazard ratio, 0.38; 95% confidence interval, 0.15- 0.93; P = .028). The MPR-ypN-based classification distinguishes postoperative outcomes and suggests that MPR ypN⁺ patients may derive benefit from adjuvant therapy.