Cholangiocarcinoma

Cholangiocarcinoma, or bile duct cancer, is a rare cancer that’s a part of the biliary tract cancers. It makes up 10–15% of all primary liver cancers globally, and around 3% of all GI cancers. Cholangiocarcinoma is often caused by unknown reasons, and it rarely has symptoms until someone has advanced disease. For this reason, many of these cancers are aggressive and hard to treat.

Incidence and mortality rates have been increasing worldwide, particularly over the past two decades, with the highest rates found in Central Asia, East Asia, and South America. Thailand, China, and South Korea have the highest incidence rates globally.

There’s hope in biomarker testing for cholangiocarcinoma patients. In about 40-50% of patients, there is at least one "actionable" biomarker, meaning there’s an FDA-approved drug that may be incorporated into your treatment plan to target your specific mutations. (This will depend on if you’re receiving first-line or second-line therapy, what the FDA approved the treatment for, your overall condition, etc.)

There are multiple targeted therapies and immunotherapies being utilized in treatment plans, and several more treatment combinations are being studied in ongoing clinical trials, which means the treatment landscape for cholangiocarcinoma is continually changing. 

What is cholangiocarcinoma?

Cholangiocarcinoma forms in the network of small ducts that carry bile from the liver to the gallbladder to the small intestine. Bile duct cancer can form in the main bile ducts outside the liver (extrahepatic) or within the liver (intrahepatic).

Types of cholangiocarcinoma

Most bile duct cancers are adenocarcinomas, cancer that forms in glands that line internal organs and make mucus and other fluids.

There are several types of cholangiocarcinoma:

• Extrahepatic perihilar bile duct cancer, also known as a Hilar or Klatskin tumor, or perihilar cholangiocarcinoma: Starts where the right and left bile ducts connect and leave the liver (an area called the hilum). This is the most common form, making up 50% of cholangiocarcinomas.
  
• Extrahepatic distal bile duct cancer, also known as distal cholangiocarcinoma: Starts after the right and left hepatic bile ducts have joined to form the common bile duct outside the liver (near the small intestine). These make up 40% of cholangiocarcinomas.
• Intrahepatic bile duct cancer, also known as intrahepatic cholangiocarcinoma (ICC/iCCA): About 10% of all cases. Starts inside the bile ducts inside the liver. This form of cancer is increasing worldwide, and is the second-most frequent type of primary liver cancer. In some very rare cases, some tumors may have tiny features of both liver cancer and cholangiocarcinoma. 

Intrahepatic cholangiocarcinoma (iCCA) is rising in Western countries, while extrahepatic cholangiocarcinoma has remained stable or declined.

Staging bile duct cancer

Cholangiocarcinoma is staged on a scale from 0–4 using the TNM staging system, but the stages are defined differently depending on where the cancer is located. Your care team will use the staging system that matches your specific subtype.

Intrahepatic (inside the liver)

• Stage 0: Abnormal cells are present but have not grown into surrounding tissue.
• Stage 1: A single tumor, confined to the liver, that has not grown into blood vessels.
• Stage 2: Either a single tumor that has grown into blood vessels, or multiple tumors, none larger than 5 cm.
• Stage 3: Multiple tumors, with at least one larger than 5 cm, or cancer that has grown into a major branch of the portal or hepatic veins, or has spread to nearby lymph nodes.
• Stage 4: Cancer has spread to nearby organs other than the gallbladder, or has spread to distant parts of the body.

Perihilar (at the junction outside the liver)

• Stage 0: Abnormal cells are present but have not spread.
• Stage 1: Tumor is confined to the bile duct wall.
• Stage 2: Tumor has grown beyond the bile duct wall into nearby fat or liver tissue, but not lymph nodes.
• Stage 3: Cancer has spread to regional lymph nodes, or has grown into branches of the portal vein or hepatic artery.
• Stage 4: Cancer has grown into major blood vessels on both sides, or has spread to distant parts of the body.

Distal (near the small intestine)

• Stage 0: Abnormal cells are present but have not spread.
• Stage 1: Tumor is confined to the bile duct wall, 5 mm deep or less.
• Stage 2: Tumor has grown more than 5 mm into the bile duct wall, or has spread to nearby tissue but not lymph nodes.
• Stage 3: Cancer has spread to regional lymph nodes.
• Stage 4: Cancer has grown into nearby major blood vessels, or has spread to distant parts of the body.

What causes bile duct cancer?

Risk factors put you at a higher risk of getting cancer. Some risk factors can be controlled with lifestyle changes, and others cannot. Older age, smoking, and obesity increase your risk of many cancers.

Just because you have a risk factor, that doesn’t mean you will get cancer. 

These are scenarios researchers have found that can increase your risk: 

• Inflammation of the bile ducts (primary sclerosing cholangitis)
• Chronic liver disease and cirrhosis (from hepatitis B or C, alcohol, or fatty liver disease)
• Bile duct cysts at birth 
• Bile duct stones/gallstones
• Parasites
• Type 1 or type 2 diabetes
• Certain inherited conditions, like cystic fibrosis and Lynch syndrome
• Exposure to toxins (rubber plants and automotive factories)

Preventing bile duct cancer

You can’t prevent cholangiocarcinoma, but you can reduce your risk. Protect yourself from viruses like hepatitis B or C.

As with every cancer, there are steps you can take to adopt a healthy lifestyle and reduce your overall cancer risk, such as maintaining a healthy weight, not smoking, and limiting or eliminating alcohol. 

Learn more about cancer prevention from the American Institute for Cancer Research.

What are some cholangiocarcinoma statistics? 

Cholangiocarcinoma is a rare disease.

About 8-10,000 people are diagnosed each year, but estimates vary and that incidence continues to increase.

Two-thirds of patients are 65 or older when diagnosed; the average age of extrahepatic cholangiocarcinoma is 72 and for intrahepatic cholangiocarcinoma it’s 70.

According to GLOBOCAN:

• The global incidence rate ranges from 0.3 to 6 per 100,000 people per year, with Thailand, China, and South Korea recording rates of 22.7, 15.0, and 13.7 per 100,000 respectively (far above the global average)
• Thailand has the highest rates globally, primarily due to widespread liver fluke infections (Opisthorchis viverrini), which cause chronic bile duct inflammation.
• Southeast Asian countries including Laos and Vietnam also report elevated rates for similar reasons.
• In Western countries, intrahepatic cholangiocarcinoma incidence is rising, linked to increasing prevalence of non-alcoholic fatty liver disease, viral hepatitis, and improved diagnostic classification.
• When intrahepatic and extrahepatic cholangiocarcinoma have spread to other parts of the body, only 2% of patients survive five years after diagnosis.
• Studies show a slight male predominance globally, particularly in regions with liver fluke infections where men face higher occupational exposure. In Western populations, the sex distribution is more balanced.

What are my odds of surviving it?

Like many other rare GI cancers, cholangiocarcinoma is often caught at late stages, when it’s most difficult to treat. Doctors use what’s called “survival statistics” to understand the likelihood of a patient beating the disease.

Detailed survival statistics are based on where the cancer is located and if it has spread:

Localized

The cancer hasn’t spread

• 24% of intrahepatic cancer patients are alive five years after diagnosis 
• 19% of extrahepatic cancer patients are alive five years after diagnosis 

Regional

The cancer spread to nearby structures or lymph nodes

• 12% of intrahepatic cancer patients are alive five years after diagnosis 
• 20% of extrahepatic cancer patients are alive five years after diagnosis 

Distant

The cancer has spread to other organs

• 3% of intrahepatic cancer patients are alive five years after diagnosis 
• 2% of extrahepatic cancer patients are alive five years after diagnosis 

What types of tests should I expect to undergo?

Doctors will likely use these tests to diagnose cholangiocarcinoma:

• Physical exam
• Blood tests checking bilirubin, liver enzymes, CA 19-9, and tumor markers
• Ultrasound
• Endoscopic retrograde cholangiopancreatography (ERCP)
• Magnetic resonance cholangiopancreatography (MRCP)

Endoscopy, MRI, PET scan, PTC, and biopsy may also be used to identify and diagnose bile duct cancer.

Ask your doctor about these additional tests—ideally before you begin treatment.

• Biomarker testing
• Genetic testing

I’m facing a diagnosis: What are my next steps?

If you’re facing a diagnosis, the GI Cancers Alliance is here for you. 

If you’re newly diagnosed, work with your doctor to create a treatment plan. It’s important to find an expert who specializes in cholangiocarcinoma and visit a major cancer center if possible.

Most cholangiocarcinoma treatment plans include a combination of:

• Immunotherapy
• Surgery (possible liver transplant for iCCA is only considered in very select cases at specialized centers under strict criteria)
• Chemotherapy 
• Radiation 
• Targeted therapy

ctDNA

A liquid biopsy is a blood test that detects fragments of tumor DNA circulating in the bloodstream, called circulating tumor DNA (ctDNA). In cholangiocarcinoma, liquid biopsy plays a particularly important role because obtaining sufficient tumor tissue through a traditional biopsy can be technically difficult. Bile duct tumors are often inaccessible or offer limited tissue samples that are not adequate for full biomarker testing.

When tissue biopsy results are incomplete or unavailable, ctDNA can serve as an alternative or complementary way to identify actionable biomarkers that may make you eligible for targeted therapies. Given that up to 40–50% of cholangiocarcinoma patients have at least one actionable biomarker, ensuring you have been fully tested is critically important, and liquid biopsy may be the tool that makes that possible.

During and after treatment, ctDNA can also be monitored over time to assess how well the cancer is responding or to detect early signs of recurrence before changes appear on imaging.

Liquid biopsy is not yet a universal standard of care in cholangiocarcinoma and is still being studied in clinical trials, but it is increasingly used at major hepatobiliary cancer centers. If your tissue biopsy did not yield enough material for complete biomarker testing, ask your care team specifically about liquid biopsy as a next step.

We strongly encourage you to get a second opinion from another trusted doctor so you feel confident moving forward.