Ghassan K. Abou-Alfa, MD: So, now that brings me to the point that sadly, as we heard from Catherine, there’s a rise in the number of patients with liver cancer. Anthony, from the perspective of oncology, are we ready for that or how do patients get referred to you? Like, how do you get patients? From whom or how do they come to you?

Anthony El-Khoueiry, MD: Yes. I think the patterns of referral differ by center depending on the practice. For me, because I work in an academic center with a liver transplant program, that tends to be the main entry door patients come in to be evaluated for liver transplant. And, unfortunately, many of them don’t qualify or don’t get a transplant or have more advanced disease and end up with medical oncology. I think the patterns of referral, again, vary from region to region as well. Nonetheless, I think what’s important with hepatocellular carcinoma is that there’s a multidisciplinary evaluation of the patients. That’s critical. And that includes the transplant surgeons, maybe hepatobiliary surgeons if they are different at the institution, interventional radiology, medical oncology, hepatology. Certainly, it’s because we are dealing with 2 diseases, the liver cirrhosis and the cancer, and because one has to take into account multiple factors in deciding on therapy. And the range of therapies is so wide, the multidisciplinary input is critical.

Ghassan K. Abou-Alfa, MD: That’s great. I’m glad you bring this up. I’m going to get back to you, but I’ll start on the left side of the different treatment approaches with Catherine and then I’ll come to you for the oncology part. Catherine, if you don’t mind, help us. If it’s a small liver lesion, great liver, what do you do? You carry on until metastatic. If you don’t mind, guide us that way.

Catherine Frenette, MD: Absolutely. First of all, I really have to agree that multidisciplinary input is critical. I don’t think that with any liver cancer patient that any one specialty can really have an idea of what’s possible with all of the different specialties. With a small liver cancer with excellent liver function, no portal hypertension or even a hepatitis B without cirrhosis, resection may be the best option for the patient depending on where the lesion is. If they’re not a resection candidate, at that point, we always ask, “OK, is transplant going to be something that’s an option for a patient?” Because we know that transplant can offer a 90% chance of cure for liver cancer, which is really remarkable. So, there are rules as far as transplant, like the Milan Criteria with 1 lesion up to 5 cm, 3 lesions up to 3 cm, no vascular invasion or metastatic disease. But most areas in the country also now are offering to downstage patients. So, even patients outside of those criteria, with appropriate treatment, can potentially get into transplant criteria and be a candidate. And oftentimes we’ll use the locoregional therapy from our interventional radiologist colleagues or radiation oncology; external beam, things like that. The medical oncologist plays an important role of deciding when it is appropriate to start with systemic therapy.

Ghassan K. Abou-Alfa, MD: Before we get to that, however, you bring another important point. If I’m not mistaken, I heard that last year the criteria for transplant were actually updated. Can you tell us a little bit about that?

Catherine Frenette, MD: So, as of last year, UNOS, the United Network for Organ Sharing, agreed that throughout the United States that downstaging would be considered to be appropriate to get extra points on the transplant list. We generally use the UCSF criteria. So, if you have 1 lesion, it can be up to 6.5 cm. If you have 2 or 3 lesions, up to 5 cm; 4 or 5 lesions, up to 3 cm; and total tumor diameter less than 9 cm. That patient then needs to be downstaged into the Milan Criteria and can get listed with exception points on the transplant list. So, that’s now a nationwide policy.

Ghassan K. Abou-Alfa, MD: I see. That’s great news in regard to our patients with HCC who are in need of a transplant. But to carry on that map that we’re drawing together, I want to come back to Ruth in regard to now a patient who really either, unfortunately, recurs after a transplant, a surgery, or after a local therapy, or to begin with, they present with metastatic disease. What will be the appropriate approach for a patient with this metastatic nature of disease?

A. Ruth He, MD, PhD: So, for patients with advanced-stage liver cancer—that includes patients with multifocal HCC who have failed, progressed on locoregional therapy, including TACE or Y-90 tail therapy, or newly diagnosed patients with multifocal disease or with vascular invasion, tumor thrombus, extrahepatic metastases—in all of those patients we should consider systemic therapy.

Ghassan K. Abou-Alfa, MD: Absolutely. That’s very important. And this brings me to the last point in regard to what you were discussing over here. Anthony, what we heard between Catherine and Ruth is really what we know as the BCLC criteria, and, if anything, there’s a very important aspect in BCLC written in a vertical fashion. Small lesion, great liver, take it out. Small lesion, bad liver, transplant. Locally advanced, not metastatic, some local therapy like embolization, Y-90, what have you. Spread out, metastatic, then, of course, systemic therapy.

But we don’t talk at all in the BCLC about any horizontal transmission because there is no doubt that a patient with a local advanced disease might get metastatic. And my question to you is, and I’m bringing this up with you specifically because you brought up this multidisciplinary approach, how do you connect in between those different layers of therapies in the line setting? How can you make sure that patients are traveling from one expert to the other based on their needs?

Anthony El-Khoueiry, MD: I think, as you said, the easiest way to accomplish that is through a multidisciplinary tumor board where the patient is reviewed initially, a treatment strategy is crafted, and then, depending on the response to therapy or the outcome, the treatment can be re-calibrated in a multidisciplinary fashion at different time points in the patient’s history, trajectory, through that with these different steps. So, without having a multidisciplinary tumor board, I think at least some communication among the various specialties will be critical.

One of the more challenging transitions, in my opinion, seems to be the transition from locoregional therapy to systemic therapy, where there are no standard criteria about when that shift should happen. And there may be different perspectives based on the different specialties. So, a discussion around that is always critical.

Ghassan K. Abou-Alfa, MD: That’s great that you bring this up, and I definitely would like to re-summarize that point by really talking about the multidisciplinary component that you just brought up. Of note, by the way, I’m going to get back to you later in the program because the collusion, if you want to call it, between the different approaches is definitely something else applying on therapy, and I’m glad at least you suggested to that discussion. And when it becomes pertinent, I’ll bring it back.

But more importantly, for all our audience, we just heard from the experts that liver cancer, unfortunately, is on the rise in the United States. And there are more and more cases of patients with liver cancer despite the great advances that were suggested by Catherine in regard to the treatment of hepatitis C. Sadly, the fatty liver disease, because of the obesity and diabetes, is actually leading more and more to an increased number of the cases per se.

In addition to that, we spoke about the nature of the therapy based on the extent of the cancer. And as I just summarized it, it is really, a small liver lesion plus great liver functionality, move on to some form of a curative surgery; a small lesion but good liver function. And, of course, Catherine reminded us of the updates to UNOS regarding beyond the criteria on what can be shrunk, then transplant. Of course, in advanced disease with regard to the different local therapies and, of course, the whole plethora of systemic therapy, that’s really the main focus of the program that we’re going to delve into in the second part over here.

Transcript Edited for Clarity