Risk factors and survival of colorectal cancer patients with RAS/BRAF gene mutations
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Purpose Compare long-term outcomes in patients with colorectal cancer with KRAS , NRAS , and BRAF gene mutations and wild-type genes. Methods The study had cohort retrospective design. The overall survival (OS) for 611 patients and disease-free survival (DFS) for 490 patients were evaluated using the Kaplan-Meier estimator as primary endpoint. Relative OS and DFS of patients with gene mutations and wild-type genes and risk factor analysis were performed as secondary endpoints. Results Patients with NRAS gene mutations had worse OS (p-value = 0.04) and patients with KRAS gene mutation had worse DFS (p-value = 0.02) both compared to wild-type genes patients. 3-year OS rate was 86%, 74% 67% and 78% and 3-year DFS rate was 50%, 34% 50% and 46% for patients with the wild-type genes, KRAS , NRAS and BRAF gene mutations, respectively. Complete cytoreduction (HR 0.20, p-value < 0.005) and stage II (HR 0.07, p-value = 0.01) of the disease were associated with a lower risk of death. A KRAS gene mutations (HR 1.61, p-value = 0.01), neoadjuvant chemotherapy (HR 1.52, p-value = 0.04), and incomplete resection (HR 1.83, p-value = 0.03) were associated with a high risk of recurrence, while stages I-III compared with stage IV (HR 0.32, p-value = 0.01; HR 0.22, p-value < 0.005; HR 0.26, p-value < 0.005) were associated with a lower risk of recurrence. Conclusion RAS/ BRAF mutations associated with worse CRC survival, however, advanced stage, incomplete cytoreduction and resection (R1) are also significant risk factors for death and CRC recurrence. Thus, early colorectal cancer diagnostic and radical and complete tumor resection allow to improve overall and disease-free survival for all patients.
