Cholangiocarcinoma: Treatment, Genomics and Supportive Care

In the second part of this two-part interview, conducted in honor of Gallbladder and Bile Duct Cancer Awareness Month, Dr. Shaun P. McKenzie spoke with CURE about bile duct cancer, or cholangiocarcinoma, outlining key differences among subtypes and how those anatomic distinctions shape surgical management. He discussed the expanding role of comprehensive genomic profiling, the integration of targeted therapies, and the importance of multidisciplinary supportive care to maintain quality of life.

Dr. Shaun P. McKenzie is board certified in general surgery and in surgical oncology, hepatobiliary surgery, and pancreatic surgery. He is a surgical oncologist with Texas Oncology Surgical Specialists–South Austin and serves as medical director for surgical oncology at Texas Oncology.

Read part one of the conversation on gallbladder cancer, here!

CURE: How do treatment strategies differ across the different anatomic categories of bile duct cancer?

McKenzie: It actually makes a big difference. If you think of the bile duct as the branches of a tree and the other cells of the liver as the leaves, that is how I explain it to my patients. You can get a cancer anywhere in the branches of the tree. If it is in the small branches in the liver, it is intrahepatic cholangiocarcinoma. If it is in the area where the largest branches come to the trunk, that is called hilar or perihilar cholangiocarcinoma. If it is near the roots, it is called distal cholangiocarcinoma.

From a surgical standpoint, they are managed quite differently, and it has a lot to do with the other structures in the area. As an example, intrahepatic cholangiocarcinoma is isolated in the liver, so removal of that portion of the liver and the lymph nodes around it is the approach, and the lymph nodes are important to understand how best to treat the patient after surgery. Perihilar disease is right where the liver splits into two lobes, and even though these cancers are small, they go into the liver quickly. In those patients, you have to remove the entire bile duct and the portion of the liver that is involved, then bring a piece of intestine up and reconnect the bile duct that is left to that intestine.

Distal cholangiocarcinoma runs through the pancreas to get to the intestine, so in those patients you have to remove part of the pancreas, the intestine, and sometimes a portion of the stomach, and then reconstruct those structures. The surgeries are very different. When it comes to treatments outside of surgery, whether that is immunotherapy, chemotherapy or newer agents, those treatments are the same because at the end of the day it is the same bile duct cell that has become cancer. The surgical management changes with the location, but not necessarily the medical management.

What is the current role of comprehensive genomic profiling in guiding targeted therapies in cholangiocarcinoma?

Cholangiocarcinoma is one of the cancers I see most frequently, and it is disheartening because we need to be better at treating it, but the story of how treatment has changed in the past few years has been one of the most exciting in cancer care. Previously, we treated this cancer with a broad approach, giving patients a couple of chemotherapy drugs that worked in similar cancers because it was rare, and we hoped for the best.

As genetic profiling has become the standard of care, we have found rare, individual targeted pathways, ways that these cells grow, and we can develop drugs that specifically break those pathways. When you combine them with other drugs, especially traditional cancer therapies, you can see exciting responses. In patients who we used to tell had two to six months, now we are talking about a minimum of one to two years. Although we wish that were longer, that is a dramatic increase in survival.

Currently, every patient with bile duct cancer undergoes genetic profiling of their cancer. In the past five years, there have been no fewer than 10 new agents developed or in discovery. It is expanding rapidly, so this is an exciting time for a cancer that we have not been able to discuss much for many years.

From a multidisciplinary perspective, what supportive care and symptom management strategies are most critical for maintaining quality of life in this patient population?

This patient population can be difficult. If we are talking about a cancer that is happening in a pipe, when pipes get blocked, things do not go well. When something gets blocked in a patient, it tends to make them very sick. Having experts in gastroenterology or radiology who can place stents to open the bile ducts so that the liver can function is very important, not just to allow treatment but to make patients feel better.

When patients become jaundiced, they do not want to eat, and they itch constantly. They lose weight and are not sleeping, so having the ability to open the bile ducts and then continue to follow them to determine whether the stent needs to be changed is a critical part of their care. Because this cancer is often found late, we encounter patients with pain and depression.

Patients read about bile duct cancer online and do not like what they see, so having mental health resources and nutritional support is key because the treatments are challenging, and patients need to be well nourished. Pain is part of the symptom burden, so having a palliative care team to manage that pain with multiple modalities is essential.

Like all cancers, it takes a team to get the patient through care, and gallbladder and bile duct cancers are no different.

What is the importance of having this awareness month and other initiatives like it?

It is huge because my area of expertise is in liver, bile duct and pancreas cancers, so I see these patients often even though the cancers are rare. I see the struggle they go through and the frustration of finding them late when there are treatments we cannot offer. That is why I emphasize not ignoring abnormalities. If it is nothing, that is the best news.

At the same time, there is hope. There are new treatments. In some centers chemotherapy is infused directly into the liver for this cancer, which was not done even 10 years ago, and those patients are living two to three years longer than patients who do not have that approach.

Progress has been slow, but it is accelerating. I want patients to stay hopeful, talk with their physician, and seek care from physicians who see this cancer frequently because it helps to have someone who knows where the cutting edge is.

Transcript has been edited for clarity and conciseness.

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