The Prognostic Impact of KRAS Mutation in Patients Having Curative Resection of Synchronous Colorectal Liver Metastases

Background: m-KRAS has been recently reported to be a significant prognostic factor in patients undergoing resection of colorectal liver metastases. This is due to the lack of response to monoclonal epithelial growth factor receptor antibodies, and potentially as a result of a more aggressive tumor biology. Methods: The National Cancer Database was queried to identify patients with known KRAS status presenting with colorectal cancer and liver metastases who underwent resection of the primary tumor and metastatic disease between 2010 and 2015. Results: A total of 2655 patients were identified of which 1116 (42%) had m-KRAS. Tumor size, lymph node involvement rates, and margin status of the primary tumor were similar between patients with m-KRAS and wild-type KRAS (wt-KRAS). In the multivariable analysis, African-American race and right-sided colon cancers were independently associated with m-KRAS (both p < 0.001). m-KRAS patients had a significantly lower overall survival (OS) than those with wt-KRAS, with a 3- and 5-year OS of 51 vs. 64% and 31 vs. 42%, respectively (p < 0.001). After adjustment for available prognostic confounders, factors independently associated with worse OS were increasing age, receipt of monoagent chemotherapy, tumor size, positive lymph node, and resection margin status of the primary tumor, right-sided cancers, and m-KRAS. Conclusions: m-KRAS is associated with worse OS in patients presenting with colorectal cancer and liver metastases undergoing resection of the primary tumor and metastatic disease. Right-sided lesions and African-American race were associated with m-KRAS. However, while right-sided remained an independent prognostic factor for OS, race did not.