From the Guidelines
Surgery is the only curative treatment for patients with cholangiocarcinoma, but it is only effective in a minority of cases, and for unresectable cases, chemotherapy with gemcitabine and cisplatin is the standard first-line treatment. Cholangiocarcinoma is a rare but aggressive cancer that develops in the bile ducts, which are tubes that connect the liver, gallbladder, and small intestine. It can occur in bile ducts inside the liver (intrahepatic), at the junction where ducts leave the liver (perihilar), or in ducts outside the liver (distal) 1. Risk factors include primary sclerosing cholangitis, liver fluke infections, bile duct stones, and certain liver diseases. Symptoms typically appear late and include jaundice (yellowing of skin/eyes), abdominal pain, weight loss, fatigue, and clay-colored stools.
Diagnosis involves blood tests, imaging studies (CT, MRI, MRCP), and often tissue biopsy. Treatment depends on cancer stage and location but primarily involves surgical resection when possible. For patients who have undergone an R0 resection and have negative regional nodes, observation alone or fluoropyrimicide chemoradiation or fluoropyrimicide or gemcitabine chemotherapy may be considered 2. For patients found to have microscopic positive tumor margins (R1), residual local disease (R2), carcinoma in situ, or positive regional lymph nodes after resection, a multidisciplinary team must review the available options on an individual basis.
Some key points to consider in the management of cholangiocarcinoma include:
- A multidisciplinary approach is required for the management of cholangiocarcinoma, involving radiological, anatomo-pathological, endoscopic, surgical, oncological, molecular, and supportive care expertise 1.
- Strongly associated risk factors for cholangiocarcinoma include congenital fibrosis, Von Meyenburg complexes, ABCB4 mutations, and LPAC syndrome, although the risk of malignancy is too low to support systematic screening.
- General risk factors like type 2 diabetes, alcohol and tobacco use, chronic viral hepatitis, and underlying liver diseases contribute to the increasing incidence of cholangiocarcinoma, particularly intrahepatic cholangiocarcinoma.
- Lynch syndrome and BRCA1/2 mutations may also be associated with the risk of cholangiocarcinoma development in some families.
In terms of treatment outcomes, the five-year survival rates vary widely from 15-50% depending on tumor location and stage at diagnosis. Early detection through screening of high-risk individuals and prompt evaluation of symptoms like jaundice are crucial for improving outcomes. Unfortunately, prognosis is often poor as most cases are diagnosed at advanced stages when complete surgical removal is not possible.
From the Research
Definition and Classification of Cholangiocarcinoma
- Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes 3.
- It is subdivided into extrahepatic and intrahepatic variants, with intrahepatic cholangiocarcinoma further differentiated into peripheral mass-forming tumors and central periductal infiltrating tumors 3.
- Cholangiocarcinoma is a heterogeneous group of neoplasms of the bile ducts, sub-classified as intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA) 4.
Risk Factors and Incidence
- The global incidence of cholangiocarcinoma has increased worldwide in recent decades 3, 4.
- Chronic inflammation of biliary epithelium and bile stasis represent the main risk factors shared by all cholangiocarcinoma sub-types 4.
- Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation 3.
Diagnosis and Treatment
- Cholangiocarcinoma diagnosis is often performed at an advanced stage when the disease is unresectable 4.
- Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy 3.
- Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases 3, 4.
- Systemic chemotherapy with gemcitabine and cisplatin represents the first treatment option for unresectable disease, but the prognosis remains poor 5, 4.
- Target therapies and immune checkpoints inhibitors have been proposed as second- or third-line treatment, alone or in combination with chemotherapy or target therapies 4.
Chemotherapy and Treatment Outcomes
- The combination of gemcitabine and cisplatin may be a safe and feasible preoperative treatment in initially unresectable locally advanced or borderline resectable cholangiocarcinoma 6.
- A case report showed that a patient with liver metastasis of intrahepatic cholangiocarcinoma achieved clinical complete response after gemcitabine and cisplatin combination chemotherapy 7.
- The standard of care in patients with unresectable tumors or metastatic disease is combination chemotherapy with gemcitabine and cisplatin 5.