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Methods for Staging HCC

Insights From: Catherine T. Frenette, MD, Scripps Green Hospital; Darren S. Sigal, MD, Scripps Green Hospital
Published: Wednesday, Apr 25, 2018



Transcript: 

Darren S. Sigal, MD: So, Dr. Frenette, there is a range of staging systems for HCC. Can you give us an overview of the ones that you think are important and the ones you utilize to make treatment decisions?

Catherine T. Frenette, MD: Sure. The staging of HCC is often a bit complicated. There are anywhere from 5 to 10 staging systems that have been reported in the literature. And whenever you know that there are that many staging systems, none of them are perfect, because if there was a perfect one, that would be the one that we use. It can be quite complicated, and the reason it’s really complicated is because when it comes to HCC, oftentimes the cancer plays just as much of a role as the cirrhosis and the underlying liver disease as far as what treatments the patients are going to be eligible for, as well as what their mortality risk is.

Something, for instance, like the TNM staging system—which, as an oncologist, you’re very comfortable using for lots of other cancers—really doesn’t work very well with liver cancer because it doesn’t take into account the underlying liver function at all. There’s the Okuda staging system and the CLIP staging system. Both of those look a lot at the underlying liver function and include things like bilirubin, albumin, INR, but then they also include how big the tumor is. And the CLIP score also includes whether it has venous invasion. You add up these numbers and it gives you an idea of what the survival of this patient is. The problem with those 2 scoring systems is that although they look closely at the underlying liver function, as far as the actual tumor, it’s really not very specific—is it greater than 50% of the liver or less than 50% of the liver?—which doesn’t really divide people very well.

Another staging system is the Memorial Sloan Kettering Cancer Center nomogram. That’s not really a staging system so much as it helps to predict if someone is going to need blood transfusions during a liver resection, which is very helpful for surgical planning, as well as for patients being educated. Probably the best staging system we have right now is the BCLC staging system—so, that’s the Barcelona Clinic Liver Cancer staging system. The way that that staging system works is, the first thing that you actually look at is the patient and the underlying liver. You look at the performance status of the patient. Are they healthy? Are they functional? What’s their ECOG score? And then you look at the Child-Pugh score to look at the liver function. Are they Child-Pugh A, no ascites, no encephalopathy, normal bilirubin, albumen, and INR? If those things are good, at that point, then, is when you actually bring in how much cancer there is. And it might be 1 lesion that’s less than 2 cm, and that’s a stage 0. If it’s 2 or 3 lesions and resectable, you go to resection; transplant is an option. The BCLC-B is more where you’re bringing in your transarterial therapies, C is the advanced patients who we’re talking about here, where we’re talking about systemic therapies. And then BCLC-D is the patients who are so advanced that, really, we’re offering them best supportive care.

Interestingly, the BCLC-D patients, they might be so advanced because of the amount of tumor, but more often it’s because their liver is very ill. They have ascites, they have encephalopathy, they’re jaundiced, or they have a poor performance status. And those patients, no matter how much cancer they have, you’re not going to change their outcomes by treating the cancer. So, the BCLC-C is nice because it has all of those things, and it guides you toward different treatments. That’s probably the staging system that we use most commonly. It’s not perfect, and there has been lots of discussion about the different sets of staging, like BCLC-B, really subdividing them into how many tumors, how big are they, do they have vascular invasion or not or metastatic disease—so, really tease out a little bit more about what their overall survival is and what the best treatment options are for these patients. These patients are a really heterogeneous group, so putting them all into a staging system is obviously quite difficult.

Darren S. Sigal, MD: We hear about MELD scores, and MELD score is not really a staging system, but how do you think about MELD score, and does it inform the stage of the patient?

Catherine T. Frenette, MD: Yes. So, the MELD score is something that was developed actually in the late ’90s, early 2000s. It was originally developed to predict who was going to do well after placement of a transjugular intrahepatic portosystemic shunt, or a TIP shunt. We then realized that the MELD score was so good at predicting 3-month, 6-month, 1-year survival that we implemented it to determine where patients would be placed on the liver transplant list. So, that’s where we are predominantly using MELD score. However, it’s really good at giving us an idea of, how bad is this person’s liver? So, the components that come into the MELD score are the bilirubin, the INR, the creatinine, and then recently we’ve added the sodium. It goes from 6 up to 40. The higher it is, the sicker your liver is. We know that, for instance, for someone who got a MELD score of 10 to 12, their liver function is really pretty good, and they’re going to tolerate a lot of the systemic treatments that we’re going to offer. However, those patients—if their MELD score is 10 to 12, not 6—they may not tolerate a resection, for instance, so that can really give us a good idea beyond just the Child-Pugh score of how somebody’s liver function is actually going.

Darren S. Sigal, MD: And the last question I have about this is the Milan criteria. It seems like the Barcelona staging system may supersede the Milan criteria. Is it incorporating it?

Catherine T. Frenette, MD: So, the Barcelona Clinic Liver Cancer staging system incorporates the Milan criteria. The Milan criteria are where we can determine if someone is going to be eligible for a liver transplant—so, that’s if you have 1 lesion and it’s up to 5 cm, or if you have more than 1, you can have up to 3, but they all have to be less than 3 cm. So, if somebody is in that criteria, they get points on the liver transplant list, and their chance of cure with a liver transplant is 90% to 95%. Now, that’s incorporated as part of the BCLC staging system. We are then, of course, moving past that a little bit now with transplant, where we’re now downstaging people where they might have a lesion that’s 6 1/2 cm, but yet with chemoembolization or Y-90, we can shrink it to less than 5 cm, and then they’re within Milan criteria and may be able to get listed.

Transcript Edited for Clarity 
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Transcript: 

Darren S. Sigal, MD: So, Dr. Frenette, there is a range of staging systems for HCC. Can you give us an overview of the ones that you think are important and the ones you utilize to make treatment decisions?

Catherine T. Frenette, MD: Sure. The staging of HCC is often a bit complicated. There are anywhere from 5 to 10 staging systems that have been reported in the literature. And whenever you know that there are that many staging systems, none of them are perfect, because if there was a perfect one, that would be the one that we use. It can be quite complicated, and the reason it’s really complicated is because when it comes to HCC, oftentimes the cancer plays just as much of a role as the cirrhosis and the underlying liver disease as far as what treatments the patients are going to be eligible for, as well as what their mortality risk is.

Something, for instance, like the TNM staging system—which, as an oncologist, you’re very comfortable using for lots of other cancers—really doesn’t work very well with liver cancer because it doesn’t take into account the underlying liver function at all. There’s the Okuda staging system and the CLIP staging system. Both of those look a lot at the underlying liver function and include things like bilirubin, albumin, INR, but then they also include how big the tumor is. And the CLIP score also includes whether it has venous invasion. You add up these numbers and it gives you an idea of what the survival of this patient is. The problem with those 2 scoring systems is that although they look closely at the underlying liver function, as far as the actual tumor, it’s really not very specific—is it greater than 50% of the liver or less than 50% of the liver?—which doesn’t really divide people very well.

Another staging system is the Memorial Sloan Kettering Cancer Center nomogram. That’s not really a staging system so much as it helps to predict if someone is going to need blood transfusions during a liver resection, which is very helpful for surgical planning, as well as for patients being educated. Probably the best staging system we have right now is the BCLC staging system—so, that’s the Barcelona Clinic Liver Cancer staging system. The way that that staging system works is, the first thing that you actually look at is the patient and the underlying liver. You look at the performance status of the patient. Are they healthy? Are they functional? What’s their ECOG score? And then you look at the Child-Pugh score to look at the liver function. Are they Child-Pugh A, no ascites, no encephalopathy, normal bilirubin, albumen, and INR? If those things are good, at that point, then, is when you actually bring in how much cancer there is. And it might be 1 lesion that’s less than 2 cm, and that’s a stage 0. If it’s 2 or 3 lesions and resectable, you go to resection; transplant is an option. The BCLC-B is more where you’re bringing in your transarterial therapies, C is the advanced patients who we’re talking about here, where we’re talking about systemic therapies. And then BCLC-D is the patients who are so advanced that, really, we’re offering them best supportive care.

Interestingly, the BCLC-D patients, they might be so advanced because of the amount of tumor, but more often it’s because their liver is very ill. They have ascites, they have encephalopathy, they’re jaundiced, or they have a poor performance status. And those patients, no matter how much cancer they have, you’re not going to change their outcomes by treating the cancer. So, the BCLC-C is nice because it has all of those things, and it guides you toward different treatments. That’s probably the staging system that we use most commonly. It’s not perfect, and there has been lots of discussion about the different sets of staging, like BCLC-B, really subdividing them into how many tumors, how big are they, do they have vascular invasion or not or metastatic disease—so, really tease out a little bit more about what their overall survival is and what the best treatment options are for these patients. These patients are a really heterogeneous group, so putting them all into a staging system is obviously quite difficult.

Darren S. Sigal, MD: We hear about MELD scores, and MELD score is not really a staging system, but how do you think about MELD score, and does it inform the stage of the patient?

Catherine T. Frenette, MD: Yes. So, the MELD score is something that was developed actually in the late ’90s, early 2000s. It was originally developed to predict who was going to do well after placement of a transjugular intrahepatic portosystemic shunt, or a TIP shunt. We then realized that the MELD score was so good at predicting 3-month, 6-month, 1-year survival that we implemented it to determine where patients would be placed on the liver transplant list. So, that’s where we are predominantly using MELD score. However, it’s really good at giving us an idea of, how bad is this person’s liver? So, the components that come into the MELD score are the bilirubin, the INR, the creatinine, and then recently we’ve added the sodium. It goes from 6 up to 40. The higher it is, the sicker your liver is. We know that, for instance, for someone who got a MELD score of 10 to 12, their liver function is really pretty good, and they’re going to tolerate a lot of the systemic treatments that we’re going to offer. However, those patients—if their MELD score is 10 to 12, not 6—they may not tolerate a resection, for instance, so that can really give us a good idea beyond just the Child-Pugh score of how somebody’s liver function is actually going.

Darren S. Sigal, MD: And the last question I have about this is the Milan criteria. It seems like the Barcelona staging system may supersede the Milan criteria. Is it incorporating it?

Catherine T. Frenette, MD: So, the Barcelona Clinic Liver Cancer staging system incorporates the Milan criteria. The Milan criteria are where we can determine if someone is going to be eligible for a liver transplant—so, that’s if you have 1 lesion and it’s up to 5 cm, or if you have more than 1, you can have up to 3, but they all have to be less than 3 cm. So, if somebody is in that criteria, they get points on the liver transplant list, and their chance of cure with a liver transplant is 90% to 95%. Now, that’s incorporated as part of the BCLC staging system. We are then, of course, moving past that a little bit now with transplant, where we’re now downstaging people where they might have a lesion that’s 6 1/2 cm, but yet with chemoembolization or Y-90, we can shrink it to less than 5 cm, and then they’re within Milan criteria and may be able to get listed.

Transcript Edited for Clarity 
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