Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer.

Abstract

The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC. Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0-18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS). A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI-high (MSI-H) and met the inclusion criteria of the final analysis. MSI-low (MSI-L) patients (n=6842) were excluded. There was a preponderance of women (55.0% [n=1311]), and 76.6% (n=1825) of patients were non-Hispanic white. The median age was 65 years (range, 19-90 years). The primary sites were the cecum (29.7% [n=707]), ascending colon (26.0% [n=620]), sigmoid colon (17.2% [n=410]), and transverse colon (10.8% [n=257]). The most common tumor grade was moderately differentiated (n=50.4% [1202]), followed by poorly differentiated (34.1% [n=813]) and well differentiated (5.1% [n=121]). High-risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n=1215) of the study population. High-risk stage III was associated with worse OS compared with low-risk stage III on univariate (P<.001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P<.001) and multivariable (P<.001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high-risk (P<.001) and low-risk (P<.001) stage III disease. Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI-H CC. An enhanced benefit was shown for high-risk stage III disease.