What Is Biliary Cancer?

February 13, 2020

Medically Reviewed By: James M. Cleary, MD, PhD

Biliary cancer is a form of cancer that develops in the bile duct system, which connects the liver, gallbladder, and small intestine, moving bile — a fluid that helps digest fats — to the small intestine. While relatively uncommon, approximately 15,000 people in the United States are diagnosed with this disease each year.

To further understand this rare disease, we spoke with James M. Cleary, MD, PhD, an oncologist in the Gastrointestinal Cancer Treatment Center at Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC).

What are the types of biliary cancer?

Biliary tract cancer is generally categorized into three groups:

  • Intrahepatic cholangiocarcinoma (bile duct cancer)
  • Extrahepatic cholangiocarcinoma
  • Gall bladder cancer

In some instances, patients with ampullary carcinoma will also be grouped together with these other subtypes. Periampullary tissue is present at the junction of the large bile duct and the small bowel.

How is biliary cancer usually diagnosed?

For intrahepatic cholangiocarcinoma, early symptoms are often not present. When symptoms develop, it is often because of a large mass in the liver that causes upper abdominal pain, or pain from metastases — the tumor spreading somewhere else. People can also lose weight and become full earlier than normal if the tumor presses on the stomach.

Similarly, extrahepatic biliary tumors that have spread also may cause pain from metastases or compression on other local organs, or weight loss. When these tumors — which occur in the bile duct that drains the liver — are found early, it’s generally because of jaundice, because it obstructs the bile duct and the skin turns yellow. Other symptoms include light-colored stool, dark urine, and itching.

Gall bladder cancer is also not commonly diagnosed at an early stage. It can sometimes be found if a patient has their gall bladder removed for infection or gall stones, but it is also diagnosed because people get symptoms from metastases. This cancer most commonly spreads to the abdominal cavity, so patients may experience abdominal pain or weight loss. Gall bladder cancer can also present with jaundice if the cancer blocks the bile ducts.

There is currently no screening test for biliary cancer, and the presenting symptoms are relatively non-specific. Many patients are diagnosed following blood work, which often includes liver function tests, or with CT scans that visualize the liver, gallbladder, and bile ducts.

Who is most at risk of developing biliary cancer/what causes the disease?

As people get older, the risk of all bile duct cancers increases.

Obesity is a risk factor for all types of biliary cancers. Smokers, women, and those who have a history of gall stones are more likely to be diagnosed with gall bladder cancer.

Infections, particularly the hepatitis viruses B and C that affect the liver, put people at a higher risk for intrahepatic bile duct cancer.

Less common infections, such as liver flukes, a parasitic infection that is common in parts of Asia, and an autoimmune inflammatory condition called primary sclerosing cholangitis (PSC), also increase the risk of both intrahepatic and extrahepatic cholangiocarcinoma.

How is the disease generally treated?

If the cancer is caught early, then surgery to remove it is commonly the first step, followed by additional therapy, such as chemotherapy and/or radiation. Surgery may include removing a portion of the liver, the biliary tree, or the gall bladder.

If the tumor cannot be removed surgically, it’s usually treated with chemotherapy, and radiation may also be used in some cases.

These are complicated cancers with complicated management approaches. We recommend patients are treated by a multidisciplinary team, where the surgeon, radiation oncologist, and medical oncologist are all involved in a patient’s care and helping them to make the best treatment decisions.

What’s on the horizon in biliary cancer research?

There are some exciting experimental medications now being tested in the treatment of biliary and gall bladder cancers.

We’ve identified several genetic mutations, particularly with intrahepatic cholangiocarcinoma, that are providing patients with new treatment opportunities.

At DF/BWCC, we have several clinical trials specifically targeting these mutations, and we now look at each patient’s tumor to see whether it carries a mutation that might be targeted with these emerging medicines. The most common of the protein alterations that we are targeting include IDH, NRAS, FGFR, HER-2, BRCA1 and BRCA2, and ATM.

There is also early data to suggest that immunotherapy may have a treatment effect for biliary cancers, and we are currently studying how these drugs may help patients with these cancers.

A recent clinical trial showed than an IDH1 inhibitor called ivosidenib improved outcomes in patients with cholangiocarcinoma. This research may lead the U.S. Food and Drug Administration to approve the drug for standard use in some patients.

To learn more about biliary cancer, visit the website for the Pancreas and Biliary Tumor Center at Dana-Farber/Brigham and Women’s Cancer Center.

About the Medical Reviewer

James M. Cleary, MD, PhD