Cholangiocarcinoma (Bile Duct Cancer) Guide

Cholangiocarcinoma is cancer that starts in the bile ducts. These are the thin tubes that carry bile from your liver and gallbladder into your small intestine. It is uncommon. Most people have never heard the word before the day they are diagnosed.

Doctors group it by where it starts. Location changes almost everything that follows.

• Intrahepatic cholangiocarcinoma begins in the smaller ducts inside the liver.
• Perihilar cholangiocarcinoma begins where the main ducts leave the liver.
• Distal cholangiocarcinoma begins lower down, near the pancreas.

Perihilar and distal tumors are together called extrahepatic. They sit in the drainage path, so they more often block bile and cause jaundice. Jaundice means yellow skin and eyes, dark urine, pale stools, and itching. Intrahepatic tumors are more often found another way. They show up because of vague belly pain, weight loss, or a scan done for some other reason.

Work-up usually includes CT and MRI with MRCP, a scan that maps the bile ducts. Blood tests check liver function. They often check the marker CA 19-9 as well. You may also have an endoscopic procedure such as ERCP or endoscopic ultrasound. These use a flexible tube to reach the ducts from inside. They can take samples. If a duct is blocked, they can also place a stent, a small tube that lets bile drain again.

Getting enough tissue matters twice over. It confirms the diagnosis. It also allows molecular testing.

The central early question is whether surgery can remove the tumor. Surgery is the only treatment that can cure cholangiocarcinoma. It is a large operation. For intrahepatic and perihilar disease it is usually a partial hepatectomy, which removes part of the liver. For distal disease it is a Whipple procedure. Only a minority of people are candidates when they are diagnosed.

Being told a tumor is unresectable, meaning it cannot be removed, is not the end of treatment. It changes which treatments are on the table. It is also a reason to ask for a second opinion at a center that does high volumes of liver and bile duct surgery.

Bile duct cancer has become one of the clearer examples of targeted treatment in gastrointestinal cancer. Ask whether your tumor has had next-generation sequencing, a test that reads many genes at once. Changes that have led to approved drugs include:

• FGFR2 fusions or rearrangements. Found mostly in intrahepatic tumors. Treated with FGFR inhibitors such as pemigatinib or futibatinib.
• IDH1 mutations. Also mostly intrahepatic. Treated with ivosidenib.
• Other findings, such as HER2 amplification, BRAF V600E, or high microsatellite instability. These may open trial or off-label options.

Results can take two to four weeks. Ask when the test was sent and when it is due back. The answer can change your next line of treatment.

Some cancers cannot be removed. For those, the long-standing chemotherapy backbone is gemcitabine with cisplatin. Trials then showed that adding an immunotherapy drug improved survival. The drug is either durvalumab or pembrolizumab. Both combinations are now approved for advanced biliary tract cancer. The gain is real but modest, and not everyone is a candidate. Ask what it means in your specific case.

Other chemotherapy combinations are used after first-line treatment. These include FOLFOX and gemcitabine with oxaliplatin. When disease is confined to the liver, local approaches are sometimes considered. These include radiation, radioembolization or ablation.

Blocked bile ducts, and the infection that follows, are the complications most likely to interrupt treatment. That infection is called cholangitis. The section below sets out what to do about it.

Palliative care alongside cancer treatment is not giving up. It is the team that manages itching, pain, appetite and fatigue while your oncologist manages the cancer. Nutrition support matters too. Bile flow affects how well you absorb fat.

Clinical trials carry unusual weight in this disease, because the field is moving quickly. Ask about them early, rather than after other options are used up. That gives you the widest set of choices.

Cholangitis is the emergency to know about, especially if you have a stent. With quick treatment the outlook is generally good. Without it, it is poor.

• Call 911 or go to an emergency department if you have fever with shaking chills alongside pain in the upper right or upper middle of your abdomen, particularly if you also feel confused, faint or very drowsy.
• Call your care team the same day if your skin or eyes turn more yellow, your urine goes dark, or your stools turn pale — a stent may be blocked.
• Call your cancer team straight away, day or night, if a temperature of 100.4°F (38°C) or higher appears while you are on chemotherapy or immunotherapy. CDC treats fever during chemotherapy as a medical emergency, because it can be the only sign of an infection that becomes life-threatening quickly. If you cannot reach them quickly, go to an emergency department and tell the staff you are having cancer treatment so you are seen straight away.
• Call your care team within a day or two if itching, nausea or belly pain is steadily worsening, or you cannot keep food down.

• MedlinePlus: Cholangitis
• NCI: Infection and Neutropenia during Cancer Treatment
• CDC: Fever and Cancer Treatment
• FDA: pembrolizumab with chemotherapy for biliary tract cancer
• NCI drug information: pemigatinib
• NCI drug information: futibatinib
• NCI drug information: ivosidenib
• NCI drug information: durvalumab
• NCI: Bile Duct Cancer Treatment (PDQ®) Health Professional Version