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

Abstract

It is known that the RAS and BRAF mutations are predictive for targeted therapies together with chemotherapy in the treatment of metastatic colon cancer and affect negatively the prognosis of the disease. In early stage cancer, however, there are limited studies in the literature about the relationship of this mutational condition with prognosis and relapse pattern of the disease. In this study, in addition to classical risk factors, we evaluated the effects of mutational status on the clinical pattern at recurrence and survival in early stage colon cancer. MethodsPatients who diagnosed with early-stage colon cancer and when following up recurrence or metastasis was detected were included in this study. Patients were divided into two groups as positive and negative RAS/BRAF mutations. Mutation analysis was performed from the early stage tissue of the patients whose mutation was positive at the time of recurrence. The relationship between mutation status and progression-free survival (PFS), overall survival (OS), and relapse pattern was analyzed. ResultsThe number of patients with positive and negative mutations in the early stage were 39 and 40, respectively. 69% of the patients in the mutant group and 70% of the patients in the wild group were in stage 3. Both OS (47.27 months vs. 67.53 months; p = 0.02) and PFS (25.12 vs. 38.13 months; p = 0.049) were statistically signi cantly lower in mutant patients. Most patients had distant metastases at the time of recurrence on both sides (61.5% vs. 62.5%, respectively). There was no signi cant difference between mutant and non-mutant patients in terms of distant metastasis and local recurrence rates (p = 0.657). In the mutation re-analysis performed from the early stage tissue of the patients with mutations in the metastatic period, 11.4% of the patients were found to have no mutations. ConclusionPresence of mutation in early stage colon cancer is associated with shorter OS and PFS. The mutational status did not have a signi cant effect on the recurrence pattern. Because of the discordance of earlystage and late-stage mutational status, it is recommended to perform mutation analysis from tissue at relapse, if possible.