A CRM-Integrated ypT Staging System Improves Prognostic Stratification Following Neoadjuvant Therapy in Rectal Cancer

Introduction:The ypT staging system has limited prognostic value after neoadjuvant therapy, as it primarily reflects only tumor characteristics alone.This study proposes a novel staging system that integrates circumferential resection margin (CRM) status with the ypT category to enhance prognostic accuracy following neoadjuvant chemoradiotherapy (nCRT) for rectal cancer.Methods: We analyzed data from 4,308 rectal adenocarcinoma patients treated with nCRT followed by surgery, using the Taiwan Cancer Registry and National Health Insurance Research Database (2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020)(2021).CRM involvement was defined as a margin 1 mm.Overall survival was assessed using multivariable Cox regression, and prognostic performance of the proposed CRM-integrated ypT staging system was compared with the American Joint Committee on Cancer (AJCC) TNM system using Harrell's c-statistic.Results: CRM involvement (1 mm) was significantly associated with worse 5-year survival (adjusted odds ratio, 0.44; 95% CI, 0.31-0.61).Due to the low rate of CRM positivity in ypT0-2 patients, a modified ypT classification was established: new ypT3 (ypT3 and CRM-), new ypT4A (ypT4A and CRM-), new ypT4B (ypT3 and CRM+ or ypT4B and CRM-), and new ypT4C (ypT4A and CRM+ or ypT4B and CRM+).This system demonstrated better prognostic discrimination than the current AJCC classification (Harrell's c-statistic: 0.756 vs. 0.752, P = 0.034).Conclusions: Incorporating CRM into the ypT stage offers survival stratification and may guide more individualized postoperative treatment strategies for rectal cancer patients after nCRT.