Association of RAS/BRAF Status and Prognosis of Metastatic Colorectal Cancer: Analysis of 1002 Consecutive Cases

This study aimed to analyze the association of RAS/BRAF status and the prognosis of patients with metastatic colorectal cancer (mCRC) based on multi-disciplinary team (MDT) treatment mode.The study retrospectively analyzed 1002 consecutive mCRC patients with different tumor RAS/BRAF status at Zhongshan Hospital Fudan University from April 2012 to December 2018. The association of RAS/BRAF status with clinicopathologic features and prognosis was analyzed.The mutation rate was 42.3% (424/1002) for RAS and 5.0% (50/1002) for BRAF. The RAS and BRAF mutations were mutually exclusive of each other. An association of RAS/BRAF status with sex (P < 0.001), age (P = 0.021), primary tumor location (P < 0.001), pathologic type (P < 0.001), differentiation (P < 0.001), metastatic organ (P < 0.001), carcinoembryonic antigen (CEA) (P < 0.001), and cancer antigen (CA)19-9 (P < 0.001) was observed. Overall survival (OS) was better for the RAS/BRAF wild-type patients than for the RAS-mutant patients, whereas the BRAF-mutant patients had the worst OS (51.0 vs 34.9 vs 18.9 months; P < 0.001). Regardless of RAS/BRAF status, metastases resection significantly improved OS (64.0 vs. 21.3 months; P < 0.001). Among the initially unresectable patients, the RAS/BRAF wild-type patients had a better conversional resection rate (32.9% vs 19.1% vs 0; P < 0.001) and a better OS (33.8 vs 23.3 vs 13.2 months; P = 0.005) than the RAS- and BRAF-mutant patients. Similarly, among the initially resectable patients, the RAS/BRAF wild-type patients had a better OS than the RAS- or BRAF- mutant patients (not assessable vs 51.7 vs 35.4 months; P = 0.005).This large-sample study showed that regardless of metastases resection or no resection, RAS and BRAF mutations were associated with a poor prognosis. Resection of metastases could bring survival benefits for patients regardless of RAS/BRAF status.