What are the treatment options for cholangiocarcinoma?

From the Guidelines

Surgery is the only curative treatment for patients with cholangiocarcinoma, and it is the preferred treatment for early-stage disease. Unfortunately, many patients are diagnosed at advanced stages when surgery is no longer an option. For these patients, chemotherapy is typically used, with gemcitabine plus cisplatin being the standard first-line regimen 1. Other chemotherapy options include 5-fluorouracil, capecitabine, and oxaliplatin. Radiation therapy may be used to shrink tumors before surgery or to relieve symptoms in advanced disease.

Treatment Options

• Surgery: removing the tumor along with surrounding liver tissue, or in some cases, liver transplantation
• Chemotherapy: gemcitabine plus cisplatin, 5-fluorouracil, capecitabine, and oxaliplatin
• Radiation therapy: to shrink tumors before surgery or to relieve symptoms in advanced disease
• Targeted therapies: pemigatinib and infigratinib for FGFR2 fusion-positive cholangiocarcinoma, and ivosidenib for IDH1-mutated disease
• Palliative procedures: biliary stenting to relieve jaundice and improve quality of life

Key Considerations

• Treatment decisions should be individualized based on the tumor's location, stage, and the patient's overall health, ideally through a multidisciplinary team approach
• Performance status is generally the most important prognostic factor, and patients with a Karnofsky status of 50 or more that are not rapidly deteriorating are usually suitable for treatment
• Good symptom control is paramount throughout and requires multidisciplinary team input
• Achieving stable disease (or lack of objective progression) in patients on therapy has value that can be translated into both length and quality of life

According to the most recent and highest quality study, liver transplantation can be effective for perihilar cholangiocarcinoma with a 65% rate of disease-free 5-year survival in highly selected patients 1. However, protocols to treat patients with cholangiocarcinoma are not widespread and are available at only a handful of transplant programs.

In terms of adjuvant therapy, additive fluorouracil-based chemotherapy has been associated with a small survival benefit after non-curative resection of gallbladder cancer 1. However, postoperative treatment after non-curative resection of cholangiocarcinoma remains controversial, and both supportive care and palliative chemotherapy and/or radiotherapy may be taken into consideration.

Overall, treatment options for cholangiocarcinoma should be individualized and based on the latest evidence, with a focus on improving quality of life and survival.

From the Research

Treatment Options for Cholangiocarcinoma

The treatment of cholangiocarcinoma depends on the stage and location of the tumor. The main treatment options are:

• Surgical resection: This is the only potentially curative treatment for cholangiocarcinoma 2, 3, 4, 5.
• Neoadjuvant therapy: This may be used to downstage the tumor before surgery 6.
• Adjuvant therapy: This may be used after surgery to reduce the risk of recurrence 3, 5.
• Liver transplantation: This may be an option for patients with localized, unresectable, lymph node-negative hilar cholangiocarcinoma 2, 4.
• Palliative care: This is used to relieve symptoms and improve quality of life for patients with advanced disease.

Surgical Treatment

The type and extent of surgical resection depend on the location and extent of the tumor. The common surgical strategies are:

• For intrahepatic tumors: tailored partial hepatectomy combined with extended hilar, suprapancreatic, celiac axis lymphadenectomy 2.
• For hilar tumors: complete resection of the extrahepatic biliary tree combined with extended hepatectomy inclusive of segment I, resection of portal vein bifurcation, and systematic N1/N2 lymphadenectomy 2.
• For distal tumors: en bloc pancreatoduodenectomy combined with complete resection of the extrahepatic bile duct below the hepatic confluence and systematic N1/N2 lymphadenectomy 2.

Challenges in Surgical Management

The challenges in surgical management of cholangiocarcinoma include:

• Diagnosis: a biopsy is typically avoided because of the risk of seeding metastases and the low yield of a brush of the bile duct 3.
• Staging: even with the best preoperative imaging, a substantial percentage of patients has occult metastatic disease detected at staging laparoscopy or early recurrence after resection 3.
• Adequate volume and function of the future liver remnant: this may require preoperative biliary drainage and portal vein embolization 3, 5.
• Complete resection: a positive bile duct margin is not uncommon because the microscopic biliary extent of disease may be more extensive than perceived on imaging 3.
• High post-operative mortality: this has decreased in very high volume Asian centres, but remains about 10% in many Western referral centres 3.

Emerging Principles in Surgical Treatment

Recent advancements in the surgical treatment of cholangiocarcinoma include:

• Refinement of staging 5.
• Improvement in liver-directed therapies 5.
• Clarification of the role of adjuvant therapy based on new randomized controlled trials 5.
• Advances in minimally invasive liver surgery 5.
• Multimodality treatment strategies, including neoadjuvant chemotherapy, stereotactic body radiation therapy, and complex liver resection with vascular reconstruction 6.