Combined microsatellite instability and BRAF gene status as biomarkers for adjuvant chemotherapy in stage III colorectal cancer.

Abstract

The clinical relevance of combined microsatellite instability (MSI) and BRAF status for adjuvant treatment in stage III colorectal cancer (CRC) remains elusive. In 405 patients with curatively resected stage III CRC, the prognostic value of combined MSI and BRAF status was assessed in four groups, as follows: high-levels of microsatellite instability (MSI-H) and BRAF-wild type, MSI-H and BRAF-mutation, microsatellite stable (MSS) and BRAF-wild type, and MSS and BRAF-mutation. Combined MSI and BRAF status provided significant prognostic stratification of disease-free survival (DFS), and was independently associated with worse DFS. The MSI-H and BRAF-wild type group had similar outcomes to stage II CRC patients, despite no benefit from 5-FU monotherapy. Further, patients in the MSS and BRAF-wild type group with stage IIIA CRC had favorable outcomes to 5-FU monotherapy, similar to those with stage II CRC. In contrast, 5-FU monotherapy was insufficient among patients in the MSS and BRAF-wild type group with stage IIIB or IIIC CRC or patients in the MSS and BRAF-mutation group with stage III CRC. The combination of MSI and BRAF status serves as both a prognostic and predictive marker and may provide much-needed guidance during the planning of therapeutic strategies.