Impact of RAS Mutations in Metastatic Colorectal Cancer After Potentially Curative Resection: Does Site of Metastases Matter?

Background: RAS mutation status is an important prognostic factor after resection of liver metastases (LiM) from colorectal cancer (CRC). The prognostic significance of RAS after resection of lung (LuM) and peritoneal (PM) metastases from CRC is unknown. Methods: Between 2005 and 2014, all consecutive patients with known RAS status who underwent potentially curative resection for LiM, LuM, or PM were evaluated. Results: A total of 720 patients with known RAS status underwent resection of LiM (n = 468), LuM (n = 102), and PM (n = 150). RAS mutations were identified in 63 and 58% of patients with LuM and PM, respectively, compared with 41% of patients with LiM (p < 0.001). Five-year overall survival (OS) after resection of PM was 45%, compared with 52% after resection of LiM (p = 0.018) and 64% after resection of LuM (p = 0.005). RAS mutations were associated with significantly worse OS after resection of LiM (p < 0.001), but did not affect OS among patients undergoing resection of LuM (p = 0.41) and PM (p = 0.65). Conclusions: RAS mutations are more prevalent among patients undergoing resection of LuM and PM than LiM but do not affect survival after lung and peritoneal metastasectomy, as they do after hepatectomy. These results suggest that the prognostic significance of RAS mutations after resection of metastatic CRC depends on the specific site of metastases.