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Identifying Staging Systems for HCC

Panelists: Ghassan K. Abou-Alfa, MD, Memorial Sloan Kettering Cancer Center; Richard S. Finn, MD, Geffen School of Medicine at UCLA; Masatoshi Kudo, MD, PhD, Kindai University Faculty of Medicine; Arndt Vogel, MD, Hannover Medical School
Published: Thursday, Aug 02, 2018



Transcript: 

Ghassan K. Abou-Alfa, MD: With this said, it brings us to an important point that we already alluded to, which is really how to stage the disease. If anything, we all agree that at the end of the day, HCC, as we suggested, is 2 problems in 1: the cancer itself and the liver functionality, disease related probably to cirrhosis or something along that line. And understandably, we use different scoring systems, different staging systems. We are used to some of them, among which, for example, is the Child-Pugh scoring, which really are 5 parameters to tell us about how good or how bad the liver is. But understandably, the 5 parameters of the Child-Pugh will lack the important parameters that are related to the cancer itself. Really, all the 5 parameters of the Child-Pugh score are related to the disease of the liver per se and not to the cancer. And, as such, there has been a lot of effort all over the world to really get a better staging system. I’ll start by asking our colleague, Dr. Masatoshi Kudo, from Japan. How do you stage patients in Japan?

Masatoshi Kudo, MD, PhD: Actually, in Japan, the BCLC stage is not so much used, but sometimes it’s useful because it’s staged in combination with liver damage plus tumor burden and shows us treatment strategy. Overall, we follow BCLC stage, but for the prognostic prediction, we use sometimes the Japan Integrating Staging, or JIS, score. And for the treatment strategy, we have another, the JSH, or Japan Society of Hepatology, treatment algorithms and guidelines. So, we follow those algorithms and treatment guideline. But overall, the basic idea is like following BCLC.

Ghassan K. Abou-Alfa, MD: I hear you. And what about in Germany or in Europe?

Arndt Vogel, MD: It depends. I think from a clinical trial point of view, it’s important to somehow categorize the patient into different categories. And the BCLC staging system is clearly most widely used, and I think we can all agree that we have early disease, intermediate disease, and advanced disease. From a clinical point of view and daily clinical life, we don’t really use it because I think it’s not really helpful. Because what we have learned, and what many trials or retrospective studies have shown, most patients are not treated according to the BCLC treatment algorithm. And this is also the case in our clinic, that in many instances we have to see the pictures, we have to see where the tumor is, how the liver function is related. And the BCLC is nice, but for treatment decision, it’s an oversimplification. It really needs a multidisciplinary tumor board. And, therefore, to be really honest, we don’t really use any staging system in the daily clinical life.

Ghassan K. Abou-Alfa, MD: That’s definitely quite fascinating to see those different point of views. We’ll ask Dr. Finn. What about at your practice? What staging system do you use?

Richard S. Finn, MD: I take a little different take than Dr. Vogel. It’s very interesting, because if you look at the other cancers we treat, is there any such diverse opinion on how to stage patients? It’s really very unique to liver cancer and, again, it represents the complexity of the disease. I think when we talk about stages, it’s why do we stage patients? And from the cancer medicine standpoint, it is prognostic. When I see a patient with these characteristics, I know what the natural history is, what to expect. And in that regard, the Barcelona criteria does that very well, and it has been developed out of the control arms of many prospective studies. It does stratify patients very well, and it has become the benchmark for most of the prospective registration strategies.

With that being said and I think where Dr. Vogel and I and the others probably come to some consensus is the orthodoxy in this stage, this is the treatment, and the treatments that are listed there. So, there’s the staging and then the treatment part. So, the staging I think is very valid and is used in my practice and others in the United States fairly frequently. But also, when it comes to assigning a patient to a specific treatment, that’s where things need to be individualized. There’s guidelines, there’s research, then there’s patient care in practice, which is what 90% of what the real world does. So, in that sense, someone might have Barcelona B, but is that strictly a TACE patient or maybe they’ll get an RFA? I think that’s where the individual attention comes into play. The other thing for staging is not only for the patient in front of you, but when I’m reading a paper, I can compare apples and oranges; that if this study looked at an efficacy endpoint in Barcelona C and this study did, too, we can try to get a sense of some consistency.

Ghassan K. Abou-Alfa, MD: I hear you loud and clear. If anything, you’ll notice that actually for those of us who got involved in the field a while ago, like decades ago, one of the big debates that we used to carry on at the time of even designing study is, which staging system should we use. If anything, you’ll notice that ultimately, we settled on Child-Pugh. If you ask me why, it’s really for no reason specifically, short of this is the only thing we agreed upon and it was the easiest to do per se. However, no doubt that we probably would differ in regard to what is the most pertinent staging system, based on the etiology of the disease. And, for example, we know very well that the CUPI, which is the Chinese University Prognostic Index from Hong Kong, is used among patients with hepatitis B, while the CLIP, or the Cancer Liver Italian Program, is really based for hepatitis C patients and is mainly used in Europe and probably is applicable in the United States as well, because we have not only hepatitis C but also alcohol-related disease. And that’s why we heard about the Japanese system, which probably is more hepatitis C specific than there is any other etiologies.

However, despite all of that, the interesting part is that we pretty much are all coming to agree that the BCLC is a great method or a great kind of cheat sheet that you can have in your hands to tell you what to do for every patient. Small disease, we take it out. Small disease, bad liver, we do transplant. Locally advanced disease, we do some form of local therapy, etc, etc. And the fascinating thing is—and I think already I heard both Dr. Vogel and Dr. Finn, both approaches very critical—that the way the BCLC is defined is really very linear. It’s from top to bottom, it’s vertical. Like “I have this, I do that.”

But, interestingly, there’s no connectivity at all in the BCLC for what if I have a patient with, let’s say, locally advanced disease but they become metastatic. What do I do? How do they move from one phase to the other? It’s not even there. So, I think it’s a little bit more complex than that. And, if anything, I’m happy to see that, yes, at the end of the day, it really depends on, as Dr. Vogel said, the multidisciplinary approach that will be very important to have the input per se. But I think we’ll all acknowledge at the same time the necessity, at least, to assess how bad or how good the liver functionality is, to be sure that you guide therapy accordingly.

Transcript Edited for Clarity 

Brought to you in part by Eisai 

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Transcript: 

Ghassan K. Abou-Alfa, MD: With this said, it brings us to an important point that we already alluded to, which is really how to stage the disease. If anything, we all agree that at the end of the day, HCC, as we suggested, is 2 problems in 1: the cancer itself and the liver functionality, disease related probably to cirrhosis or something along that line. And understandably, we use different scoring systems, different staging systems. We are used to some of them, among which, for example, is the Child-Pugh scoring, which really are 5 parameters to tell us about how good or how bad the liver is. But understandably, the 5 parameters of the Child-Pugh will lack the important parameters that are related to the cancer itself. Really, all the 5 parameters of the Child-Pugh score are related to the disease of the liver per se and not to the cancer. And, as such, there has been a lot of effort all over the world to really get a better staging system. I’ll start by asking our colleague, Dr. Masatoshi Kudo, from Japan. How do you stage patients in Japan?

Masatoshi Kudo, MD, PhD: Actually, in Japan, the BCLC stage is not so much used, but sometimes it’s useful because it’s staged in combination with liver damage plus tumor burden and shows us treatment strategy. Overall, we follow BCLC stage, but for the prognostic prediction, we use sometimes the Japan Integrating Staging, or JIS, score. And for the treatment strategy, we have another, the JSH, or Japan Society of Hepatology, treatment algorithms and guidelines. So, we follow those algorithms and treatment guideline. But overall, the basic idea is like following BCLC.

Ghassan K. Abou-Alfa, MD: I hear you. And what about in Germany or in Europe?

Arndt Vogel, MD: It depends. I think from a clinical trial point of view, it’s important to somehow categorize the patient into different categories. And the BCLC staging system is clearly most widely used, and I think we can all agree that we have early disease, intermediate disease, and advanced disease. From a clinical point of view and daily clinical life, we don’t really use it because I think it’s not really helpful. Because what we have learned, and what many trials or retrospective studies have shown, most patients are not treated according to the BCLC treatment algorithm. And this is also the case in our clinic, that in many instances we have to see the pictures, we have to see where the tumor is, how the liver function is related. And the BCLC is nice, but for treatment decision, it’s an oversimplification. It really needs a multidisciplinary tumor board. And, therefore, to be really honest, we don’t really use any staging system in the daily clinical life.

Ghassan K. Abou-Alfa, MD: That’s definitely quite fascinating to see those different point of views. We’ll ask Dr. Finn. What about at your practice? What staging system do you use?

Richard S. Finn, MD: I take a little different take than Dr. Vogel. It’s very interesting, because if you look at the other cancers we treat, is there any such diverse opinion on how to stage patients? It’s really very unique to liver cancer and, again, it represents the complexity of the disease. I think when we talk about stages, it’s why do we stage patients? And from the cancer medicine standpoint, it is prognostic. When I see a patient with these characteristics, I know what the natural history is, what to expect. And in that regard, the Barcelona criteria does that very well, and it has been developed out of the control arms of many prospective studies. It does stratify patients very well, and it has become the benchmark for most of the prospective registration strategies.

With that being said and I think where Dr. Vogel and I and the others probably come to some consensus is the orthodoxy in this stage, this is the treatment, and the treatments that are listed there. So, there’s the staging and then the treatment part. So, the staging I think is very valid and is used in my practice and others in the United States fairly frequently. But also, when it comes to assigning a patient to a specific treatment, that’s where things need to be individualized. There’s guidelines, there’s research, then there’s patient care in practice, which is what 90% of what the real world does. So, in that sense, someone might have Barcelona B, but is that strictly a TACE patient or maybe they’ll get an RFA? I think that’s where the individual attention comes into play. The other thing for staging is not only for the patient in front of you, but when I’m reading a paper, I can compare apples and oranges; that if this study looked at an efficacy endpoint in Barcelona C and this study did, too, we can try to get a sense of some consistency.

Ghassan K. Abou-Alfa, MD: I hear you loud and clear. If anything, you’ll notice that actually for those of us who got involved in the field a while ago, like decades ago, one of the big debates that we used to carry on at the time of even designing study is, which staging system should we use. If anything, you’ll notice that ultimately, we settled on Child-Pugh. If you ask me why, it’s really for no reason specifically, short of this is the only thing we agreed upon and it was the easiest to do per se. However, no doubt that we probably would differ in regard to what is the most pertinent staging system, based on the etiology of the disease. And, for example, we know very well that the CUPI, which is the Chinese University Prognostic Index from Hong Kong, is used among patients with hepatitis B, while the CLIP, or the Cancer Liver Italian Program, is really based for hepatitis C patients and is mainly used in Europe and probably is applicable in the United States as well, because we have not only hepatitis C but also alcohol-related disease. And that’s why we heard about the Japanese system, which probably is more hepatitis C specific than there is any other etiologies.

However, despite all of that, the interesting part is that we pretty much are all coming to agree that the BCLC is a great method or a great kind of cheat sheet that you can have in your hands to tell you what to do for every patient. Small disease, we take it out. Small disease, bad liver, we do transplant. Locally advanced disease, we do some form of local therapy, etc, etc. And the fascinating thing is—and I think already I heard both Dr. Vogel and Dr. Finn, both approaches very critical—that the way the BCLC is defined is really very linear. It’s from top to bottom, it’s vertical. Like “I have this, I do that.”

But, interestingly, there’s no connectivity at all in the BCLC for what if I have a patient with, let’s say, locally advanced disease but they become metastatic. What do I do? How do they move from one phase to the other? It’s not even there. So, I think it’s a little bit more complex than that. And, if anything, I’m happy to see that, yes, at the end of the day, it really depends on, as Dr. Vogel said, the multidisciplinary approach that will be very important to have the input per se. But I think we’ll all acknowledge at the same time the necessity, at least, to assess how bad or how good the liver functionality is, to be sure that you guide therapy accordingly.

Transcript Edited for Clarity 

Brought to you in part by Eisai 
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