# A pathological classification for predicting recurrence and guiding adjuvant therapy in esophageal squamous cell carcinoma following neoadjuvant immunochemotherapy: a two-center cohort study

## TL;DR

This study proposes a new classification system to predict recurrence and guide treatment for esophageal cancer patients after immunochemotherapy.

## Contribution

A novel pathological classification system based on tumor regression grade and ypN status to guide adjuvant therapy decisions in ESCC patients.

## Key findings

- TRG and ypN status were identified as independent predictors of recurrence-free survival.
- A subgroup (TRG0-1 ypN+) showed significant survival improvement with adjuvant therapy.
- Four prognostic subgroups were defined based on TRG and ypN status.

## Abstract

Neoadjuvant immunochemotherapy (nICT) has emerged as a promising treatment modality for locally advanced esophageal squamous cell carcinoma (ESCC). However, optimal post-nICT adjuvant strategies remain undefined, and a classification system that integrates both prognosis and recurrence patterns to guide treatment decisions is currently lacking.

This retrospective study enrolled 283 patients with locally advanced ESCC who underwent nICT with R0 resection between January 2019 and December 2023 at two participating institutions. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included recurrence patterns, overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS). Survival curves were generated using the Kaplan-Meier method. Propensity score matching was employed for group comparisons and a Cox proportional hazards model was used to identify prognostic factors.

The pathological complete response (pCR) and major pathological response (MPR) rates were 22.6% and 52.3%, respectively. Multivariate analysis identified the tumor regression grade (TRG) and ypN stage as independent predictors of RFS. Both ypN status and TRG were key determinants of recurrence patterns. Based on this, patients were stratified into four subgroups: Group 1 (TRG0-1 ypN0), Group 2 (TRG0-1 ypN+), Group 3 (TRG2-3 ypN0), and Group 4 (TRG2-3 ypN+). This classification demonstrated significant prognostic stratification, with Group 1 having the best prognosis and Group 4 having the worst prognosis. In the entire matched cohort, adjuvant therapy did not significantly improve survival. However, subgroup analyses revealed that adjuvant therapy was associated with a significant improvement in RFS in Group 2 (TRG0-1 ypN+)(HR = 0.16, 95% CI 0.06–0.42, P<0.001).

The proposed classification system based on TRG and ypN status effectively stratified the prognosis of patients with ESCC after nICT. This classification enabled the identification of a specific subgroup (TRG0-1 ypN+) that may benefit from postoperative adjuvant treatment.