CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis

Aims/Background: Diagnosis of early cholangiocarcinoma (CC) in patients with primary sclerosing cholangitis with available radiological methods is very difficult. This type of tumor is the second most common cause of mortality after liver failure in these patients. The recognition of CC is important for the selection of patients for, and the results of, liver transplantation (Ltx). In this study our aim was to investigate the value of measuring cancer markers (CA 19-9 and CEA) in patients with PSC for early diagnosis of CC. Methods. 72 PSC patients who were followed at our institution for a long period were included in the study; 9 with CC and 63 without CC. Furthermore, nine patients with CC but without concomitant PSC were included, as well as 24 patients with various cholestatic liver diseases. Serum levels of CA 19-9 and CEA were measured, in 39 PSC patients without CC, on multiple occasions. Moreover, bile was collected during a diagnostic ERCP from 20 patients for measurements of CA 19-9 and CEA. Results: In those PSC patients without CC during the follow-up and with more than one year of follow-up, 15 patients had increased Values of CA 19-9 (>37 ng/ml) on some of the occasions. Four of them demonstrated large fluctuations (more than 100 ng/ml difference at different occasions) in serum levels of Ca 19-9. A significant correlation between high CA 19-9 values and serum alkaline phosphatase levels was observed in these patients. The sensitivity of CA 19-9 in detecting CC in PSC patients was only 63%. The sensitivity of CEA and the combination of CA 19-9 and CEA (marker product; King's College formula) were still lower (33%) although the specificity was relatively high (85%). Bile levels of the tumor markers did not demonstrate any clinically useful differences between the different patient groups. Conclusions: Tumor markers as a diagnostic tool in diagnosing CC in patients with PSC are unfortunately not as valuable as previously reported. The serum levels of CA 19-9 can rise temporarily in association with a "biochemical relapse" of PSC (increased values of serum alkaline phosphatase). The marker product of CA 19-9 and CEA has a low sensitivity but a relatively high specificity for the detection of CC in PSC patients.