Precision Medicine: A New Frontier for Advanced Cholangiocarcinoma - Episode 2

Heterogeneity of CCA


Ghassan Abou-Alfa, MD, MBA: Martin, actually, the fascinating part is that…I would like to know your opinion. Are we lumping 3 diseases and maybe more, being intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and some who call them biliary cancers? Is this like really a delineation? Is there a difference between the 3 or no difference? What shall we call those diseases?

Martin Gutierrez, MD: It’s fascinating how the field has been evolving. A learning that we have done over the last few years have differentiated the diseases in a molecular-driven FGFR and specifically for intrahepatic carcinomas in IDH1 versus the extrahepatic cholangiocarcinoma and gallbladder disease. So clearly the molecular biomarkers are going to be a key point for us to move forward and dissect the disease and the treatments.

Ghassan Abou-Alfa, MD, MBA: Andrea, would you agree then that probably rather than lumping everything in biliary tumors, we should be more specific nowadays and define the specific disease—intrahepatic, extrahepatic, etc?

Andrea Wang-Gilliam, MD, PhD: I completely agree. I think we’re moving into a molecular age in which tumors should be less anatomically important but more molecularly emphasized. I also emphasize that we should really push for molecular testing in those patients and try to obtain the biopsy. Sometimes we don’t do it, but we really should.

Ghassan Abou-Alfa, MD, MBA: Absolutely. So back to you, Andrew. We’ll jump a little back to pathology. If anything, the intrahepatic cholangiocarcinoma, of course, is a continuum with extrahepatic. Let’s assume as a theoretical example that you have a tumor right in the edge. It can be called intrahepatic cholangiocarcinoma, but it could be also called extrahepatic cholangiocarcinoma. But let’s assume that the genetic makeup of it is suggestive more of an intrahepatic cholangiocarcinoma. How do you treat it, or how do you look at it?

Andrew Zhu, MD, PhD: As you correctly pointed out, making the distinction of intrahepatic cholangiocarcinoma versus perihilar cholangiocarcinoma is not always straightforward on the clinical side. This is because sometimes they actually present very similarly just based on the pure anatomic location, which may not actually be sufficient enough. But I think with the sophisticated tools and also with a molecular signature that we’re having today, we have more confidence calling it intrahepatic cholangiocarcinoma as opposed to perihilar. With regard to the implication, all tumor types that we mentioned—regardless of whether it’s intrahepatic cholangiocarcinoma, perihilar, gallbladder—the surgical treatment is the key thing that we will consider.

In other words, making the initial distinction for the surgical intervention probably will have relatively little bearing in the first time. This is because you have to think about whether you can get the tumor out or not. That’s the first question. We will discuss that for selective perihilar cholangiocarcinoma with small tumor burden. We do have some very early data with the role of liver transplantation. But that’s very specific and only for a very small subtype of perihilar. For the majority we still talk about surgery.

Ghassan Abou-Alfa, MD, MBA: Fair enough. We’re going to hold off on that because we’re going to talk quite a bit on the interventions, and I’m sure we’re going to dissect it a little further in details.

Transcript Edited for Clarity