Circulating tumor cells are associated with diffuse spread in stage IV colorectal cancer patients

Background: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States when combining both genders. Circulating tumor cells (CTCs) are a prognostic marker for stage IV CRC patients. We hypothesized that CTC quantity varies among stage IV CRC populations. Methods: Blood (7.5 ml) was prospectively collected from 90 stage IV CRC patients. EpCAM+ CTCs were analyzed with the FDA-approved CellSearchR system. CRC tumors were immunohistochemically stained for EpCAM expression. Imaging and clinicopathological data were collected. Statistical analysis was performed using correlation analysis, Kruskal-Wallis, Fisher exact, and log-rank test. Results: CTCs were detectable in 36/90 (40%) patients. Diffuse CRC metastases were associated with the highest CTC prevalence (24/40 [60%]), in contrast to limited lung (2/19 [11%]) or liver (10/31 [32%]) metastases (P = 0.027). The overall mean CTC number was 2.0 (range 0-56.3). The mean CTC number in patients with diffuse metastases was significantly higher (3.7 [SE M ± 1.7, range 0-56.3]) than with limited lung metastases (0.1 [± 0.1; range 0-1]) or liver metastases (0.9 [± 0.3, range 0-7.0]) (P = 0.001). CRC tumors were consistently expressing EpCAM. CTC numbers did not correlate with serum CEA levels or other routine clinical parameters (P = N.S.). Patients with diffuse metastases had the poorest overall survival (P = 0.0042). Conclusions: CRC patients with diffuse metastases have the highest number of CTCs, in contrast to limited metastases to the liver or lungs. Future studies should correlate CTCs with recurrence patterns in patients with resected CRC lung or liver metastases to investigate whether CTCs represent micrometastatic disease causing early relapses.