Effect of mutational status on disease behavior and treatment outcome in patients with metastatic colorectal cancer: intratumor heterogeneity and mutational status.

BACKGROUND

Nowadays, the outcomes of metastatic colorectal cancer (mCRC) have considerably improved. Genetic studies evaluating mutational status are important in the personalized therapy era to understand disease heterogeneity, disease behaviors, and treatment outcomes.

METHODS

This multicenter retrospective study evaluated 360 patients with mCRC treated at three oncology centers in Saudi Arabia and Egypt between February 2011 and December 2015. Patients were treated with bevacizumab and cetuximab according to guidelines. Therapy outcome, time to progression, and disease-associated death were assessed. mutational status was evaluated by testing exons 12 and 13.

RESULTS

Approximately 220 (61.1%) cases were of wild-type , whereas mutation was noted in 38.9%. mutation was common in the descending colon, whereas a low incidence of the mutation was observed in the ascending colon (P<0.001). Among patients with mutation, 64.3% initially presented as emergency cases with obstruction/perforation (P=0.002), and 62.9% had hepatic or pulmonary metastasis. The progression-free survival (PFS) was 10.7 months. Cases without mutation showed a higher PFS than did those with mutation (mean PFS: 11.5 9.6 months, P=0.001). The overall survival was 23.2 months. The survival varied considerably according to type: patients without mutation survived for 25.0 months and those with mutation survived for 19.6 months (P<0.001). Disease-related death occurred in 132 (36.7%) cases, approximately 57.1% of them (80 cases) had mutations (P=0.001).

CONCLUSIONS

A major association between mutational status and both disease behavior and treatment outcomes was found in this study. Patients with mutation show advanced disease presentation, with lower PFS and overall survival.