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

Niccolo Allievi, Paolo Goffredo, Alan F. Utria, Michele Pisano, Elia Poiasina, Alessandro Lucianetti, Paige Zhou, Imran Hassan


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% hadm-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.