Understanding cholangiocarcinoma

Patient Voice spoke with Dr. Jennifer Knox to learn more about cholangiocarcinoma (CCA), a group of cancers that occur in the bile ducts. She discusses the ongoing challenges associated with treating rare cancers and why it’s a promising time for Canada’s CCA community.

Photography by Patient Voice.

Dr. Knox is a Professor of Medicine at the University of Toronto, staff medical oncologist, and Co-Director for the Wallace McCain Centre for Pancreatic Cancer at the Princess Margaret Cancer Centre.

1.What is cholangiocarcinoma (CCA)?

CCA is a rare group of cancers that arise in the biliary tree.

The biliary tree is also known as the biliary tract or the biliary system of the liver, and it refers to the organs and ducts that produce and transport bile (an important digestive fluid that breaks down fats during digestion and carries away waste). Specifically, CCA cancers affect the bile ducts. These ducts carry bile from the liver (where it’s produced) to the gallbladder (where it’s stored), through the pancreas and into the small intestine, where it aids in digestion.

The different types of CCA include intrahepatic CCA (which forms in the smaller bile ducts inside the liver) and extrahepatic CCA (which forms in the larger bile ducts outside the liver). The latter includes hilar CCA (the most common form of the disease, which forms in the bile ducts that lead out of the liver and join with the gallbladder). These CCA cancer types are related in their pathology and differ from other gastrointestinal cancers.

2.When and how is CCA typically diagnosed?

It varies greatly depending on the specific type. 

Extrahepatic CCA often presents with right upper abdominal pain and jaundice. Hilar CCA often causes unexplained liver tests or jaundice. Intrahepatic CCA may also present with abnormal liver tests and/or pain, or may be picked up incidentally as a liver mass on a CT scan or ultrasound and then determined to be CCA with a biopsy.

3.How has understanding of this disease and its treatment evolved throughout your career? 

Over the years, the medical community has gained a much better understanding of the biology of these cancers. We now know that the different types of CCA aren’t all the same and that knowing the type of CCA may affect treatment options. This has led to more genomic testing and the discovery of more treatment targets. Essentially, the adoption of precision medicine or personalized medicine is resulting in much better outcomes for some patients who have “druggable” mutations.

Unfortunately, diagnostic methods for CCA haven’t changed very much during my career. CCA is typically hard to diagnose as the bile ducts are deep inside the body, and so tumours are often missed during routine physical examinations. They may also be very hard to biopsy. Additionally, there are no reliable blood tests or other screening tests that can be used to detect CCA in asymptomatic patients. Our main goal as a community is to find CCA earlier.

In terms of treatment, there was nothing standard to recommend when I first started treating CCA patients 22 years ago. Throughout my career, we’ve developed standard chemotherapies that prolong life for patients with advanced disease. Newer chemotherapy combinations, and perhaps immunotherapy, may help even further. There has also been an improvement in surgical standards and adjuvant chemotherapy for the 20 to 30 percent of patients who are diagnosed with local or resectable disease, which means disease that is more likely to be cured.

“We now know that the different types of CCA aren’t all the same and that knowing the type of CCA may affect treatment options. This has led to more genomic testing and the discovery of more treatment targets.”

4.What kinds of challenges are associated with developing novel medicines to treat rare cancers?

Unfortunately, rare cancers don't receive much attention in medicine or in the media. They don’t get as many research dollars assigned to them when compared to diseases with a higher incidence. It’s also considerably harder to conduct larger randomized clinical trials with rare tumours. Even small trials with convincing evidence that a treatment is helping a rare tumour population are often ignored or dismissed as not having enough data to effect real change in practice or to impact funding policies.

Once new medicines are developed, in some cases they may become available to patients through a clinical trial in Canada. If the trial result is positive, and suggestive of improvement, the treatment is reviewed by Health Canada. Once approved by Health Canada, patients must wait for their province to decide on funding if they don’t have private insurance or another funding pathway. Unfortunately, the wait for approval, review, and funding can take years.

5.Why is it a hopeful time for Canada’s CCA community?

Despite all the challenges, the global medical community has new data supporting novel treatment options for CCA patients with advanced disease. There’s also growing evidence that certain new molecules can target rare gene mutations or rearrangements in some CCA patients, leading to meaningful cancer control. We now have several whereas we had none only a few short years ago.

This medical progress makes a strong case for the argument that all CCA patients should get their tumour sequenced (also known as genomic profiling) through a research, public, or commercial assay, as this may help identify new treatment options.

New drug combinations have also moved into the pre-surgical setting. There are now trials to study whether we can cure more patients with early-stage disease or secure better outcomes with localized therapies such as surgery or radiation. With all these advances and innovations, it’s a hopeful time for the Canadian CCA community.

Founded in 2006, the Cholangiocarcinoma Foundation is a global non-profit organization. Our mission is to find a cure and improve the quality of life of cholangiocarcinoma patients. To learn more, visit

This initiative was supported by Incyte Biosciences Canada. This page and the editorial themes covered were developed by Patient Voice.