College of American Pathologists Tumor Regression Grading System for Long-term Outcome in Patients with Locally Advanced Rectal Cancer.

Abstract

BACKGROUND\nNCCN s Rectal Cancer Guideline Panel recommends American Joint Committee of Cancer and College of American Pathologists tumor regression grading (AJCC/CAP TRG) system to evaluate pathologic response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC). Yet, the clinical significance of AJCC/CAP TRG system has not been fully defined.\n\n\nMETHODS\nThis was a multicenter, retrospectively recruited, and prospectively maintained cohort study. Patients with LARC from one institution formed the discovery set, and cases from external independent institutions formed validation set to verify the findings from discovery set. Overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were assessed by Kaplan-Meier analysis, log-rank test, and Cox regression model.\n\n\nRESULTS\nThe discovery set (940 cases) found, and validation set (2156 cases) further confirmed, that inferior AJCC/CAP TRG categories were closely correlated with unfavorable survival (OS, DFS, LRFS and DMFS), and higher risk of disease progression (death, accumulative relapse, local recurrence and distant metastasis) (all P<0.05). Significantly, pairwise comparison revealed that any two of four TRG categories had the distinguished survival and risk of disease progression. After propensity score matching, AJCC/CAP TRG0 category (pCR) patients treated with or without adjuvant chemotherapy displayed similar survival of OS, DFS, LRFS and DMFS (all P>0.05). For AJCC/CAP TRG1-3 categories cases, adjuvant chemotherapy treatment significantly improved 3-year OS (90.2% vs. 84.6%, P<0.001). Multivariate analysis demonstrated AJCC/CAP TRG system was an independent prognostic surrogate.\n\n\nCONCLUSIONS\nAJCC/CAP TRG system, an accurate prognostic surrogate, appears ideal for further strategizing adjuvant chemotherapy for LARC.\n\n\nIMPLICATIONS FOR PRACTICE\nNCCN recommend the AJCC/CAP TRG 4-category system to evaluate the pathologic response to neoadjuvant treatment for patients with locally advanced rectal cancer. However, the clinical significance of AJCC/CAP TRG system had not yet been clearly addressed. In this study, we found for the first time that any 2 of 4 AJCC/CAP TRG categories had the distinguished long-term survival outcome. Importantly, adjuvant chemotherapy may improve the 3-year overall survival for AJCC/CAP TRG1-3 category, whereas not for AJCC/CAP TRG0 category patients. Thus, AJCC/CAP TRG system, an accurate surrogate of long-term survival outcome, is useful in guiding adjuvant chemotherapy management for rectal cancer.