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 wit h primary sclerosing cholangitis with available radiological methods is ver y difficult. This type of tumor is the second most common cause of mortalit y after liver failure in these patients. The recognition of CC is important for the selection of patients for, and the results of, liver transplantati on (Ltx). In this study our aim was to investigate the value of measuring c ancer 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 lo ng period were included in the study; 9 with CC and 63 without CC. Furtherm ore, nine patients with CC but without concomitant PSC were included, as we ll 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 o ccasions. Moreover, bile was collected during a diagnostic ERCP from 20 pat ients for measurements of CA 19-9 and CEA. Results: In those PSC patients w ithout 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 occasi ons. Four of them demonstrated large fluctuations (more than 100 ng/ml diff erence at different occasions) in serum levels of Ca 19-9. A significant co rrelation 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 o f 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 t he tumor markers did not demonstrate any clinically useful differences betw een the different patient groups. Conclusions: Tumor markers as a diagnosti c tool in diagnosing CC in patients with PSC are unfortunately not as valua ble as previously reported. The serum levels of CA 19-9 can rise temporaril y in association with a "biochemical relapse" of PSC (increased values of s erum 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 P SC patients.