The survival outcome of patients with metastatic colorectal cancer based on the site of metastases and the impact of molecular markers and site of primary cancer on metastatic pattern

Background: Pattern of spread in patients with metastatic colorectal cancer (mCRC) is variable and may reflect different biology in subsets of patients. This is a retrospective study to explore the outcome of patients with mCRC based on their site of metastasis at diagnosis and to explore the association between tumor characteristics [KRAS/RAS, BRAF, mismatch repair (MMR) status, site of primary] and the site of metastasis. Methods: Patients from two Australian databases were divided into six groups based on site of metastasis at time of diagnosis of metastatic disease; lung-only, liver-only, lymph node-only or any patients with brain, bone or peritoneal metastases. Primary endpoint was overall survival (OS) of each cohort compared with the rest of the population. A Mantel-Haenszel chi-squared test used to explore the association between site of metastasis and selected tumor characteristics. Results: Five thousand nine hundred and sixty-seven patients were included. In a univariate analysis, median OS was significantly higher when metastases were limited to lung or liver and shorter for those with brain, bone or peritoneal metastases (p < .001) in both datasets. BRAF mutation was strongly associated with peritoneal metastases (relative risk = 1.8, p < .001) with lower incidence of lung (RR = 0.3, p = .004) and liver (RR = 0.7, p = .005) limited metastases. Lung-only metastases were more frequent with KRAS/RAS mutation (RR = 1.4, p = .007). Left colon tumors were associated with bone (RR = 1.6, p < .001) and lung-only metastases (RR = 2.3, p = .001) while peritoneal spread was less frequent compared with right colon tumors (RR = 0.6, p < .001). Rectal cancer was associated with brain, bone and lung metastases (RR = 1.7; p = .002, 1.7; p < .001, 2.0; p < .001). Liver-only metastases were less frequent in deficient MMR tumors (RR = 0.7, p = .01). Conclusion: Survival duration with mCRC is related to the site of metastases with lung limited disease showing a more favorable survival outcome compared to other single metastatic site disease. The BRAF mutation and primary rectal cancer were associated with poor prognostic metastatic sites.