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

TL;DR

This study introduces a new staging system for rectal cancer that combines tumor stage with margin status to better predict patient outcomes after treatment.

Contribution

A novel CRM-integrated ypT staging system is proposed to improve prognostic accuracy after neoadjuvant therapy.

Findings

CRM involvement was significantly associated with worse 5-year survival.

The new staging system showed better prognostic discrimination than the AJCC system.

The modified ypT classification includes CRM status for more accurate survival stratification.

Abstract

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.

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 (2011-2021). 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.

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).

Incorporating CRM into the ypT stage offers survival stratification and may guide more individualized postoperative treatment strategies for rectal cancer patients after nCRT.

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