A Novel TRG-N Prognostic Classification System for Esophageal Cancer Undergoing Neoadjuvant Therapy Followed by Esophagectomy

Objective: To develop a new prognostic classification system centered on tumor regression grade (TRG) and ypN stage that can effectively stratify overall survival (OS) of esophageal cancer patients undergoing neoadjuvant therapy (NAT) followed by R0 esophagectomy. Summary Background Data: Although the prognostic value of combining TRG and ypN stage has been demonstrated, a prognostic classification system integrating these factors, trained using large-scale data, remains unavailable. Methods: Data from the Netherlands Cancer Registry (2015–2022) were analyzed. A new TRG-N prognostic classification system for OS was developed by grouping patients based on cN stage, ypN stage, and TRG. The prognostic performance of the TRG-N classification was compared with the 8 th edition AJCC ypTNM classification using 4 comparative metrics (Log-rank χ², Linear trend χ², Akaike’s Information Criterion [AIC], and C-index). Results: A total of 3,193 patients were included. Among patients with adenocarcinoma, the TRG-N classification showed superior Linear trend χ² and AIC to the ypTNM classification. However, the Log-rank χ² of the TRG-N classification was inferior to that of the ypTNM classification, with no significant difference in the C-index ( P -value=0.206) between the two systems. Among patients with squamous cell carcinoma, the TRG-N classification significantly outperformed the ypTNM classification in Log-rank χ², Linear trend χ², AIC, and C-index ( P -value=0.018). Conclusion: The TRG-N classification demonstrated comparable prognostic performance to the AJCC ypTNM classification for esophageal adenocarcinoma but showed superior prognostic value for esophageal squamous cell carcinoma, making it a potentially more effective tool for risk stratification in esophageal cancer patients.