Precision Medicine: A New Frontier for Advanced Cholangiocarcinoma - Episode 4

Prevalence of CCA


Ghassan Abou-Alfa, MD, MBA: With this said, however, we have another question to talk about—who gets cholangiocarcinoma or who gets gallbladder cancer? We’ll start with you, Teresa. Who are your patients who you see here in Barcelona, Spain, at Vall d’Hebron Institute that really has cholangiocarcinoma? How common is it, and who are they?

Teresa Macarulla, MD, PhD: Yes. In Western countries, it is around 2 cases per 100,000, so more or less this is the incidence. Sadly, we don’t know exactly which are the risk factors, at least in our country. It’s a complicated issue to know the reason for cholangiocarcinoma.

Ghassan Abou-Alfa, MD, MBA: But relatively rare. Martin, less or more in New Jersey?

Martin Gutierrez, MD: Well, Jersey is one specific state...of the United States. In the United States we see the same incidence. It’s only 3% of all GI [gastrointestinal] malignancies that we see. So it’s probably 1, 2, to 3 per 100,000 patients—42,000 diagnosed in the United States at any given time on a weekly basis.

Ghassan Abou-Alfa, MD, MBA: Andrew, you have quite a bit of expertise and understanding of the disease cholangiocarcinoma in other parts of the world. Tell us about cholangiocarcinoma in Asia.

Andrew Zhu, MD, PhD: Yeah. The etiology actually varies, depending on the geographic region. I agree that for the majority of the patients with this type of cancer, we actually have very limited understanding about the underlying risk factors. Short of the primary sclerosing cholangitis, perhaps underlying cirrhosis, and some congenital anatomic disorders, for the majority of it we don’t know anything about why they develop the disease. However, if you look at the global platform in the endemic area, particularly in Thailand, parasitic infection clearly is a well-established risk factor. In regions in Southeast Asia, particularly in Thailand, you actually have the endemic cholangiocarcinoma associated with actually the parasitic infections.

Ghassan Abou-Alfa, MD, MBA: Sure, the fluke worm.

Andrew Zhu, MD, PhD: Yeah, the fluke worm. I think for the majority, we have actually very limited understanding. Having said that, I think there is a lot of very interesting epidemiologic work ongoing, particularly highlighting the association of the cholangiocarcinoma with cirrhosis related to, for example, NASH [nonalcoholic steatohepatitis] or even hepatitis. It seems like, at least for intrahepatic cholangiocarcinoma, if you have any increased risk to develop cirrhosis, your risk perhaps also increases with the development of cholangiocarcinoma. But I think a lot of work needs to be done in this space.

Ghassan Abou-Alfa, MD, MBA: Along that line, Andrew, I totally agree with you on that and who gets cholangiocarcinoma. I’ll go back to Andrea. Do we have any understanding of those cholangiocarcinoma, for example, that Andrew referred to that are related to the fluke worm that we see mainly in Southeast Asia and the ones that you see in the Western Hemisphere? Do you have an understanding about any differences there? Where do we stand on this?

Andrea Wang-Gilliam, MD, PhD: Yeah. I actually want to defer that question to Andrew because he’s the expert of liver fluke. I personally practice here and am not seeing anybody with liver fluke cholangiocarcinoma. I think pathologically they are different. But I’m actually not sure whether the response to treatment is that much the same.

Ghassan Abou-Alfa, MD, MBA: Well, what we know so far is that genetically there could be some differences, even though they are not really super well delineated. There have been some data that came out of Thailand with regard to the genetic makeup of the tumor. In regard to responses, we also don’t have a delineation about the understanding of what they can or cannot respond to. Truly the treatment so far is we treat them all the same way. However, it brings us to another point with regard to the cholangiocarcinoma. Specifically, as Andrew suggested, there is a potential for the cholangiocarcinoma to be combined with HCC [hepatocellular carcinoma]. I know that your center at Washington University has a lot of interest in that.

Andrea Wang-Gilliam, MD, PhD: Yes.

Ghassan Abou-Alfa, MD, MBA: Tell us more about this.

Andrea Wang-Gilliam, MD, PhD: Over years with our superior pathologist, we realized there may be an entity that’s mixed type where you have in the cells have some cholangiocarcinoma histology as well as HCC histology. We call it mixed type or biphenyl. Now the question is how do you treat it? In general, we think that the cholangio is more aggressive, so we generally treat it as part of a cholangiocarcinoma. But this is like a truly recognized entity now.

Ghassan Abou-Alfa, MD, MBA: Absolutely. What we heard again is that the incidence of cholangiocarcinoma is relatively low in the western hemisphere. However, as we heard from Dr Zhu, there are certain pockets in the world that sadly have high incidence of cholangiocarcinoma. Among this high incidence rate is Southeast Asia, driven mainly in data coming from Thailand. But other countries are definitely influenced by that as well—including southern parts of China and as with Laos and Vietnam. This is mainly driven by the fluke worm. The best understanding that we have is that yes, there could be some delineation that is yet to be dissected further. But at the moment, the therapies are the same regardless what the etiology is.

Along that line, we spoke very briefly about a combination of hepatocellular carcinoma-cholangiocarcinoma, and I totally agree with Andrea that potentially taking care of the cholangiocarcinoma component is critical because of the aggressive nature of that disease.

Transcript Edited for Clarity