Cholangiocarcinoma – current treatment options

Friman S (2011) Cholangiocarcinoma--current treatment options. Scand J Surg, 100(1):30-34

Summary

In intrahepatic CCA, HR remains the treatment of choice whereas with concomitant liver disease such as cirrhosis or primary sclerosing cholangitis (PSC), LT is the only option.

Cholangiocarcinoma (CCA) is a malignant disease of the epithelial cells in the intra- and extrahepatic bile ducts. While still a rare malignant disease, CCA is the second most common primary malignancy of the liver. The incidence is increasing; especially the incidence of intrahepatic CCA (1).

Predisposing risk factors for CCA

Primary Sclerosing Cholangitis: At the present time, brush cytology is the most effective diagnostic tool for the identification of CCA in PSC-patients with a dominant bile duct stricture (9).

Hepatitis B and C: More recently, hepatitis viruses (HBV, HCV) have been considered as risk factors for intrahepatic CCA; this could be an explanation for the increased incidence of CCA over the last two decades (12).

Treatment

ICC: In a recent large series reported by the Berlin group, there were R0 resections in 71% of 195 patients with a 5-year overall survival of 22% (17). Comparably, the group from Essen recently reported that the rate of R0 resections among their series of 83 patients was 64%. The overall 5-year survival was 21%; with 30% survival for the group which had an R0 resection (18).

There have been recent reports of an approximate survival rate of 30% after 5 years in this population (7, 19).The scarcity of transplantable organs, along with the procedure’s relatively low survival rate, makes this treatment a marginal choice.

LIVER TRANSPLANTATION FOR CCA: CCA continues to generate controversy as an indication for LT; in many centres CCA continues to be considered as a contraindication. In contrast, a retrospective review of our patients from Norway, Sweden and Finland showed us that with a high degree of selection an over 50% 5-year survival rate can be achieved (20). This favourable 5-year survival rate suggests that CCA need not be considered as a contraindication and that candidate selection criteria should be re-evaluated.

From our report, it is evident that the 5-year survival rate for patients who received transplants prior to 1995 raises questions. The early reports from Kings College and Hannover had a 5-year survival rate after transplantation for CCA of 0–20% (23, 24). Our recent data in the Nordic countries are comparable with those of other publications showing a 5-year survival rate of about 30–40% after LT (19, 20). Surgical resection is still the treatment of choice whenever feasible and a radical R0-resection can achieve similar 5- year survival data. 

There has been some controversy if there exists any difference in outcomes after LT of extra- or intrahepatic CCA. In studies where the majority of the patients have concomitant PSC, a majority have intrahepatic CCA. Shimoda and co-workers from the Los Angeles group did not see any difference in survival rates between intra- and extrahepatic CCA patients (25). Our results from the Nordic series are similar, indicating that there is no difference in survival between the two cohorts. 

PHARMACOLOGICAL THERAPY: CCA has been shown to be resistant to common chemotherapy. Numerous drugs have been tested alone and in combination. The response rate has been unacceptably low. Gemcitabine has been suggested as an alternative for patients with unresectable CCA;  survival benefit remains to be proven in a randomised controlled trial (29). Concerning the value of biological agents like sorafenib, which has an effect on HCC (30), only a few pilot studies are available and the reponse rate  reported so far is not impressive (31).

PALLIATIVE BILIARY STENTING: Patients that are not candidates for radical surgical treatment often benefit from palliative treatment of their bile duct obstructions. The biliary stenting can be performed with endoscopic technique or with percutaneus transhepatic approach. Self expanding metal stents are most commonly used since these seem to remain patent longer than do polyethylene stents (32).