Central, But Not Peripheral, Circulating Tumor Cells are Prognostic in Patients Undergoing Resection of Colorectal Cancer Liver Metastases

Background: Colorectal cancer liver metastases (CRLMs) are potentially curable with resection, but most patients recur and succumb to their disease. Clinical covariates do not account for all outcomes. Circulating tumor cells (CTCs) are prognostic in the primary and metastatic settings of breast, prostate and colorectal cancer (CRC), and evolving evidence supports their role in CRLMs. Our objective was to determine whether CTCs in peripheral (PV) and hepatic venous (HV) compartments are associated with disease-free survival (DFS) and overall survival (OS) post-CRLM resection. Methods: CTCs were measured by CellSearch assay from intraoperative HV and PV samples from 63 patients who underwent CRLM resection from June 2007 to August 2012 at a single center. DFS and OS were primary endpoints. Results: HV CTCs > 3 were associated with shorter DFS and OS, but not PV CTCs, although no significant difference was found between CTC measurements in the two compartments. By univariate analysis, CRC stage and site, CRLM recurrence, and hepatic capsule invasion were also associated with OS, but only HV CTCs and CRC site were significant by multivariate Cox. Only HV CTCs were associated with DFS by multivariate analysis. Cases with elevated HV CTCs had hepatic vein invasion and lymph node metastases, and were younger with larger tumors. Conclusions: Elevated HV CTCs are prognostic for DFS and OS following CRLM resection. Clinicopathologic features associated with HV CTCs are identifiable preoperatively and should be considered in CRLM surgical decision making. We found no evidence that PV CTCs are prognostic in this setting.