What are the treatment options for cholangiocarcinoma?

Treatment Options for Cholangiocarcinoma

Surgery is the only curative treatment for cholangiocarcinoma, though it is only successful in a minority of patients, with 9-18% five-year survival for proximal bile duct lesions and 20-30% for distal lesions. 1

Classification and Staging

Cholangiocarcinoma (CCA) is classified into three main types based on anatomical location:

1. Intrahepatic cholangiocarcinoma (iCCA)
2. Perihilar cholangiocarcinoma (pCCA or Klatskin tumor)
3. Distal cholangiocarcinoma (dCCA)

Comprehensive staging is essential and should include:

• Chest radiography
• CT abdomen (unless MRI/MRCP already performed)
• Laparoscopy (to detect peritoneal or superficial liver metastases)

Surgical Management

Resectable Disease

The surgical approach depends on tumor location:

• Perihilar (Klatskin) tumors (based on Bismuth classification):

  • Types I and II: En bloc resection of extrahepatic bile ducts and gallbladder, regional lymphadenectomy, and Roux-en-Y hepaticojejunostomy
  • Type III: Above plus right or left hepatectomy
  • Type IV: Above plus extended right or left hepatectomy
  • Consider removal of liver segment 1 with stages II-IV

• Distal cholangiocarcinoma: Pancreatoduodenectomy

• Intrahepatic cholangiocarcinoma: Resection of involved segments or lobe of the liver

Surgical outcomes:

• Median survival for intrahepatic CCA without hilar involvement: 18-30 months
• Median survival for perihilar tumors: 12-24 months
• Five-year survival rates: up to 40% for intrahepatic CCA, 20% for hilar CCA, and 20-30% for distal extrahepatic CCA

Important Considerations for Surgery

• Patient suitability should be guided by medical risk factors rather than age
• Tumor-free margins and absence of lymphadenopathy are the most important positive prognostic indicators
• Inadequate biliary drainage may increase the risk of sepsis and complicate surgery
• For potentially curable disease, open or percutaneous biopsy is not recommended due to the risk of tumor seeding

Liver Transplantation

• Liver transplantation is currently contraindicated for unresectable cholangiocarcinoma 1
• It is typically associated with rapid recurrence and death within three years
• In pilot studies, liver transplantation following preoperative chemoirradiation has shown promising results in carefully selected patients and may be appropriate within clinical trials

Adjuvant Therapy

Recent evidence suggests benefit from adjuvant chemotherapy:

• Capecitabine is increasingly used as adjuvant therapy following curative resection 2, 3

Palliative Management for Unresectable Disease

Biliary Drainage

• Biliary obstruction in unresectable disease is best palliated by insertion of a biliary endoprosthesis rather than surgical bypass 1
• Adequate biliary drainage improves survival
• Routine biliary drainage before assessing resectability should be avoided except in cases of acute cholangitis

Systemic Therapy for Advanced Disease

• First-line treatment: Gemcitabine and cisplatin combination 2, 3
• No established second-line chemotherapy regimen

Emerging Targeted Therapies

Recent advances in molecular profiling have identified potential therapeutic targets:

• IDH-1 (isocitrate dehydrogenase) mutations
• FGFR-2 (fibroblast growth factor receptor) fusions
• Immune checkpoint inhibitors targeting PD-1, PD-L1, and CTLA-4 2, 3

Common Pitfalls and Caveats

1. Diagnostic challenges: CCA can be difficult to differentiate from metastatic adenocarcinoma. Thorough investigation is needed to exclude primary tumors from other sites (pancreas, stomach, breast, lung, colon).

2. Biopsy timing: For potentially resectable disease, surgical assessment of resectability should be established prior to biopsy due to the risk of tumor seeding.

3. Late presentation: Most patients present with advanced disease when curative options are limited. The global incidence of CCA has increased worldwide in recent decades 2.

4. Treatment nihilism: Previous treatment nihilism has been replaced by active clinical research and a better understanding of molecular mechanisms 3.

5. Multifocal disease: Bile duct cancers may be multifocal (5%), which can complicate surgical management.

The management of cholangiocarcinoma continues to evolve with advances in molecular profiling and targeted therapies. For optimal outcomes, patients should be managed at specialized centers with multidisciplinary expertise in hepatobiliary malignancies.