Cholangiocarcinoma (CCA) is the second most common cause of primary liver cancer. Currently, useful prognostic and predictive biomarkers for CCA do not exist, resulting in diagnosis at an advanced stage with no effective treatment options. Therefore, the prognosis associated with this malignancy is generally grim.
Circulating tumor cells (CTCs) in the peripheral blood are associated with poor survival of patients with breast, prostate, or colon cancer. Due to this correlation of the effect of CTCs on various types of cancer, Mayo Clinic researchers hypothesized that CTCs are also associated with poor survival of patients with CCA. The study was published in the journal Hepatology.
“CTCs have clinical relevance, and ongoing technologic advances will enable molecular characterization with the hope of identifying relevant phenotypic or genotypic alterations that will guide and individualize effective systemic therapy,” said Minetta Liu, M.D., Consultant in the Department of Oncology and the Department of Laboratory Medicine and Pathology at Mayo Clinic and author on this paper.
The study included 88 patients with CCA who were enrolled at Mayo Clinic between June 2010 and September 2014. To detect CTCs in peripheral blood, researchers used the FDA-cleared CellSearch™ test, which captures and enumerates CTCs.
In the study, 7.5 mL of whole-bloodwere processed within 96 hours of venipuncture for CTC enumeration. A cutoff of 5 CTCs per 7.5 mL blood has been established in breast and prostate cancer, and a cutoff of 3 CTCs has been established in colorectal cancer. For this study, the initial analysis focused on a cutoff of 5 CTCs with plans to analyze lower cutoffs as needed. Results of CTCs greater than or equal to 2 per 7.5 mL of blood were obtained in 17 percent of the patients, and CTCs greater than or equal to 5 per 7.5 mL of blood were obtained in 9 percent of the patients. The median survival was significantly shorter in patients using either CTC threshold (i.e., greater than or equal to 2 per 7.5 mL of blood, or greater than or equal to 5 per 7.5 mL of blood), and the prognostic value was retained in both univariate and multivariate analyses.
Patients with CTCs greater than or equal to 2 per 7.5 mL of blood had a 2.5 fold-increased risk of earlier death compared to patients with CTCs less than 2 per 7.5 mL of blood. Similarly, patients with CTCs greater than or equal to 5 per 7.5 mL of blood had a 4.1 fold-increased risk of earlier death compared to patients with CTCs less than 5 per 7.5 mL of blood.
“Our findings suggest that CTC enumeration at the time of initial presentation might differentiate those patients with localized CCA who have an excellent prognosis and are best served by curative resection alone versus those who are likely to recur and should undergo curative resection followed by adjuvant chemotherapy,” said Dr. Liu.
The results also indicate that CTC enumeration might identify those patients with advanced CCA who will most likely benefit from palliative chemotherapy versus those patients whose prognosis is so poor that a focus on best supportive care is most appropriate.
Given that CTCs were associated with more aggressive tumor characteristics and independently associated with overall survival in patients diagnosed with CCA, the study suggests that CTC enumeration may be useful for guiding treatment decisions in this patient population.
“Molecular characterization of these clinically relevant cells may help facilitate more appropriate drug therapy selection and improve outcomes in the future,” said Dr. Liu. “It should be noted, however, that clinical validation studies are required before CTC enumeration may be considered for use in the routine clinical setting for cholangiocarcinoma.”