The Effect of RAS/BRAF Mutation Status on Prognosis and Relapse Pattern in Early Stage Colon Cancers

Purpose: It is known that the RAS and BRAF mutations are predictive for targeted therapies in treating metastatic colon cancer and negatively affect the prognosis of the disease. However, there are limited studies in early-stage colon cancer about the relationship of this mutational condition with the prognosis and relapse pattern of the disease. In this study, we evaluated the effects of mutational status on the clinical pattern of recurrence and survival in early-stage colon cancer in addition to classical risk factors.

Methods: Patients with early-stage colon cancer at the first time of diagnosis and developing recurrence or metastasis on following up were included in this study. Patients were divided into two groups according to the at the time of relapse RAS/BRAF mutation status: mutant or non-mutant/wild types. Then, mutation analysis was performed again from the early-stage tissue of the patients if available. The relationship between early-stage mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed.

Results: The number of patients with mutant and non-mutations in the early stage was 39 and 40, respectively. Mutant and non-mutant patients with stage 3 disease were similar (69% and 70%, respectively). OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically significantly lower in mutant patients, respectively. Most patients had distant metastases on both sides at recurrence (61.5% vs. 62.5%, respectively). There was no significant difference between mutant and non-mutant patients regarding distant metastasis and local recurrence rates (p = 0.657). A discordance of 11.4% between early-stage and late-stage tissue mutation status.

Conclusion: The presence of mutation in early-stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a significant effect on the recurrence pattern. Because of the discordance of early-stage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse.