The association of KRAS mutation with primary tumor location and survival in patients undergoing resection of colorectal cancers and synchronous liver metastases

Background: Recent evidence suggests that a mutation in the KRAS gene has a significant impact on the clinical behavior and prognosis of patients with metastatic colorectal cancer. The KRAS mutation (m-KRAS) has been associated with decreased survival among patient undergoing treatment with a curative and palliative intent. This is believed to be secondary to a reduced response to anti-EGFR chemotherapy agents and a more intrinsically aggressive biology. The aims of this study were to identify risk factors for m-KRAS in patients with curatively resected colorectal cancer and synchronous liver metastases and to assess its association with disease-specific survival (DSS). Methods: The Surveillance, Epidemiology and End Results (SEER) Database was surveyed for patients undergoing resection of colorectal cancer and synchronous liver metastases from 2010 to 2015. Results: A total of 806 patients were included, of which 40% had m-KRAS. Right-sided primary lesions (OR 2.56, 95% CI: 1.90-3.44, P<0.001) and African-American ethnicity (OR 1.58, 95% CI: 1.05-2.40, P=0.03) were independently associated with m-KRAS on multivariable analysis. Compared to wild-type KRAS (wt-KRAS), m-KRAS was associated with decreased 3- and 5-year DSS (59% vs. 50% and 29% vs. 21%, respectively, P=0.024). After adjusting for confounders, a decreased DSS was observed in patients with right-sided lesions (HR 1.68, 95% CI: 1.32-2.12, P<0.001), while m-KRAS was associated with a trend toward decreased DSS (HR 1.15, 95% CI: 0.91-1.46, P=0.24). Conclusions: In patients undergoing surgical resection of colorectal cancer and synchronous liver metastases, m-KRAS was associated with right-sided lesions and African-American ethnicity. Compared to wt-KRAS, m-KRAS was associated with a reduced DSS. Additionally, right-sided lesions were an independent negative prognostic factor for DSS.