Multidisciplinary Treatment Strategies for Hepatocellular Carcinoma - Episode 2

Determining Factors in HCC Prognosis

Transcript: Ghassan K. Abou-Alfa, MD: If I get a call from one of our colleagues asking me for an opinion on liver cancer, I’d say, “How cirrhotic is the patient or the liver?” Tell us, is it 2 problems in 1, separate, or the same thing? Tell us more.

Amit Singal, MD: HCC [hepatocellular carcinoma] can be a difficult cancer to treat because exactly as you said, it is 2 issues that each patient has: it’s the underlying cirrhosis and the HCC. The problem is that the degree of liver dysfunction can actually impact what treatments you can deliver effectively in patients who have HCC. When you think of this, we typically grade the degree of liver dysfunction using the Child-Pugh score, which incorporates your lab variables and the presence of ascites and hepatic encephalopathy, and you receive a grade A, B, or C.

But if you have severe liver dysfunction, that’s actually what’s going to drive your prognosis, and there’s actually very little utility in treating HCC outside of liver transplantation. That’s when we see patients for whom we have to consider the degree of liver dysfunction and available liver disease treatments. Katie brought up the point of hepatitis-B [HBV] related HCC. If you see somebody who has hepatitis-B related HCC, it’s important to consider treating that underlying hepatitis B to help maintain their liver function so you can effectively treat the HCC long term.

Ghassan K. Abou-Alfa, MD: Along that line, Farshid, is there any specific way, or methodology, or even an instrument or a scoring system, that you use for assessing the cirrhosis component. Which one would you say is most appropriate?

Farshid Dayyani, MD: That’s a very appropriate question because, as Amit said, we are dealing with 2 enemies here: the underlying liver disease and the cancer. I see, now, everybody is aware of this, where several classifications are globally applied, and they have different criteria. I think in the United States, at least in our practice based on the clinical trials we do, we most commonly use the Barcelona Clinic Liver Cancer [BCLC] staging system to attribute the appropriate treatment strategy for a patient. For clinical trials or day-to-day assessment of liver function, we apply, most of the time, the Child-Pugh scoring system. And obviously the anatomic staging TNM [Tumor, Node, Metastasis] that goes into all the classifications. Those are the ones that we most commonly use with ECOG [Eastern Cooperative Oncology Group] or Karnofsky performance status.

Ghassan K. Abou-Alfa, MD: As you know, I would say the Child-Pugh score, as Amit said as well, is not necessarily fully applicable in regards to HCC, but we use it because it’s the best we have in hand, like the BCLC staging system in advanced disease. What do you think?

Katie Kelley, MD: There’s advantages and disadvantages to every scoring and staging system we have. I think for the Child-Pugh scoring system, the challenge is the subjectivity of certain metrics, including the ascites and the encephalopathy, which, you know, can vary according to the day; clinicians also have variable metrics systems. There are new tools being proposed to try to circumvent this like the ALBI [albumen, bilirubin] score, which you know well of, which is a purely mathematical calculation of albumen and bilirubin, and has shown to outperform the Child-Pugh score in some prospective studies. So that’s a consideration as we move forward in our trials to perhaps validate that further in independent cohorts.

Back to the BCLC staging system, I think it’s really a division that’s been borne out of the historical treatments we’ve used for liver cancer. Now that we have so many systemic therapies to work with, in addition to the therapies we’re finding to be more efficacious, we really need to parse out more the entity of intermediate and advanced score. It’s not so clean as the B versus C grade. It turns out there’s a huge disparity between a patient who’s a Barcelona B with 4 tumors or a Barcelona B with 50 tumors. There are certainly other scores that try to subgroup this, but as we have more tools at our disposal, in the systemic therapy world in particular, we really need to refine the metrics we use.

Ghassan K. Abou-Alfa, MD: I totally agree. If anything, what I’m hearing is that number one, sadly, liver cancer is a global problem, and, in particular, it’s on the rise in the United States. Furthermore, there are four main risk factors: hepatitis b, which drives most of the disease worldwide; hepatitis C [HCV], which occurs mostly in the western hemisphere, including the United States; and alcohol-related cirrhosis which we now call fatty liver disease.

As you already heard, HCC is really 2 problems in 1: the cancer itself, as well as the liver sources, een though it’s not necessarily present all of the time; however, most of the time it is present. If anything, assessing the cirrhosis is as important as a secondary extent of the cancer. Of course the extent of cancer can go by HCC staging or whichever scale you’re comfortable with, but in regard to the extent of cirrhosis, there is continued debate regarding death.

Almost 20 years ago there was a settlement among different players regarding HCC in accepting that we will move on with the Child-Pugh score. It was given the green light, and that’s why most of the data, as Farshid just mentioned, is based on this scoring system, even though the 5 parameters, which are the bilirubin and albumin level, the PT INR [prothrombin time; international normalized ration], and the ascites. As Katie said, there is also encephalopathy, which is also clinical.

As you can see, those 5 parameters do not lead to the cancer itself; it’s all about the liver function. That’s why some other systems have evolved accordingly. But there are way too many of them. It’s confusing, really, to all of us, in deciding which scoring system to use, even though there could be some nuances here and there.

I would sat the BCLC system is more of a manual; it’s not necessarily a system that is robust, especially when it comes to advanced disease, because it really lumps everything and everybody in the same category. An important aspect of the BCLC system, despite it, is that it can give you advice for what to do with a patient; it’s good vertically but not horizontally, as we move with the disease from one place to another.

I always like to say that maybe the BCLC system works great when we talk about it in the extreme left, i.e., for resectable disease, which can be cured, but it doesn’t perform well with systemic disease per se.

Transcript Edited for Clarity