The Diagnostic Approach to HCC

Transcript:Ghassan K. Abou-Alfa, MD: I’d like to go back to the point about the disease. I’ll start by asking our colleagues in oncology. Katie, I’ll start with you. So you get the call. You have a patient with HCC who has a tumor that may be HCC [hepatocellular carcinoma], with high EPI [exocrine pancreatic insufficiency]—the risk factors are there, but there’s no biopsy. Would you biopsy?

Katie Kelley, MD: That’s a great question. I think particularly now that we have multiple systemic therapies to choose from, both for HCC, as well as the alternate diagnosis of biliary tract cancer, I increasingly feel that having a tissue diagnosis is critically important for patients who might be candidates for multiple lines of therapy, especially if patients don’t meet imaging criteria for diagnosis.

Occasionally there may be a tumor that’s really inaccessible for biopsy. In this case, if their radiology findings meet criteria for ASLD [adenylosuccinate lyase deficiency] radiographic diagnosis with arterial enhancement in portal venous washout in a patient with known underlying fibrosis or cirrhosis, we will accept imaging diagnosis, even for advanced disease. But I think our paradigm at our institution, and what I’m seeing in colleagues around the world, is that, as we have more tools to treat advanced disease, particularly across types of tumors in the liver, and not just HCC but also biliary tract, it’s imperative to make sure we know what the histology is.

Ghassan K. Abou-Alfa, MD: Amit, I totally agree with Katie. If anything, I always need a tissue biopsy. Convince me why I should not do it with tissue.

Amit Singal, MD: Clearly I’m going to be the odd man out here.

Ghassan K. Abou-Alfa, MD: That’s why I’m asking.

Amit Singal, MD: Yes.

Ghassan K. Abou-Alfa, MD: Remember we are 3 for 1.

Amit Singal, MD: Taking it from a hepatology perspective, like Katie mentioned: when you have these classic criteria of arterial enhancement and delayed washout, this has a 95% to 97% positive predictive value for being HCC in the setting of cirrhosis.

Now I agree with you that as we have more therapies, particularly as this field evolves, we’re going to have biomarkers at some point. We have research trials that require biopsy. We are starting to use biopsy more with the idea that we’re starting to understand the cancer better. And I think that when we talk to the patients about this, we can tell with 95% to 97% certainty that this is HCC. We just can’t say it with 100% certainty. I do, incidentally, mention the research aspect of this as well. So I think that we have started to use it more. I don’t think we require it for treatment but I think it’s something that will help the field evolve over the next several years.

Ghassan K. Abou-Alfa, MD: Fair enough. Farshid, other than the biopsy, nowadays patients come to you and say, “I want to know the genetic makeup of my tumor. I want to know which mutations are present.” They look also to see if it’s MSI-high. All of these questions come into play. So what’s your standard? What is your recommendation in regards to HCC and genetic screening?

Farshid Dayyani, MD: Well, again, in 2019, the treatment of liver cancer is clinical research; that’s where all the revolutions come into play. I think part of the reason we’re using this outdated classification is so we can all speak the same language and make comparisons. Building on that, getting tissue and blood samples to further characterize the tumors to understand the tumor better—that’s paramount, especially at our center. In my practice, every single patient will have a circulating tumor DNA sent. We biopsy as much as we can just to learn about a tumor, not necessarily for diagnosis, or to put them on a clinical trial.

The traditional markers—PD-L1 [programmed death-ligand 1] and MSI [micro-satellite instability]— haven’t been as established as ACCS [1-aminocyclopropane 1-carboxylate synthase homolog] , as in other cancers, but obviously we are looking for further predictive and prognostic biomarkers. So I think at a minimum, try to make a platform to build upon. That’s part of the reason why we try to obtain as much information from each patient as possible.

Ghassan K. Abou-Alfa, MD: Fair enough. So the question of biopsy, it really goes back to the idea of patients who are at risk for developing HCC. You want to make sure that you screen them. Usually the standard screening will consist of ultrasound; there’s a debate.

As you can imagine, when an ultrasound is done, you might see a lesion. The idea is you can’t keep poking needles into somebody’s liver to see what the biopsy shows, which is why we the radiologic criteria was mentioned, as we just heard from Amit.

Interestingly, however, things are evolving. At the moment, we have a much better understanding of the disease. To summarize, HCC is not necessarily as pure of an entity as we think it is. For example, a combination of HCC with cholangiocarcinoma can happen. We better know about that, which is why biopsy will probably be necessary. To think about cholangiocarcinoma as an entity, it really has nothing to do with the risks factors of HCC, because a patient with HBV can get cholangiocarcinoma.

In addition to that, we heard the opposing view that we still need a better understanding of the tumor. We don’t have a direct applicability for that material that we can obtain from a biopsy. Nonetheless, as thins evolve, it will be important to understand what the tumor consists of so we can treat accordingly. You’ll see how confusing it is when we come to talking about therapies, per se.

Transcript Edited for Clarity