Impact of Single-organ Metastasis to the Liver or Lung and Genetic Mutation Status on Prognosis in Stage IV Colorectal Cancer

This analysis of patients in the National Cancer Database demonstrates that patients with single-organ lung metastases had worse survival than single-organ liver metastases, even when accounting for primary tumor location. Furthermore, KRAS mutation and microsatellite instability status are of prognostic importance in selected patients with single-organ metastases, and testing should be considered in all patients with stage IV colorectal cancer. Background: The impact of primary tumor site on overall survival in patients with stage IV colorectal cancer (CRC) with single-organ metastases to the liver or lung has not been studied. Furthermore, the prognostic significance of commonly tested genetic variants such as KRAS mutation and microsatellite instability (MSI) are not well-described in this population. Materials and Methods: This National Cancer Database was used to identify 38,328 patients with CRC that presented with synchronous metastases to the liver or lung between 2010 and 2014. The primary outcome was overall survival, and groups were compared using Kaplan-Meier analyses and Cox proportional hazard models. Results: On unadjusted analysis, median survival was significantly longer for patients with lung metastases compared with those with liver metastases for left-sided (27 vs. 25 months; P = .02) and right-sided CRC (19 vs. 15 months; P < .001), whereas rectosigmoid and rectal cancers showed no difference. On multivariate analysis, patients with liver metastases demonstrated worse survival compared with those with lung metastasis (hazard ratio, 1.37; 95% confidence interval, 1.31-1.43; P < .001). These trends were confirmed in patients that received chemotherapy but did not have their primary tumor or metastases resected. In patients with genetic testing, both KRAS mutants and MSI tumors had worse survival in left-sided and rectal tumors with liver metastases, but had similar survival to KRAS wild type tumors and microsatellite stable tumors, respectively, across other primary site and metastatic patterns. Conclusions: For patients with single-organ metastases to the liver or lung, primary tumor site has an impact on overall survival. Further, KRAS mutation and MSI status are of prognostic importance in selected patients with single-organ metastases. (C) 2019 Elsevier Inc. All rights reserved.