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HCC: Criteria for Resection and Adjuvant Therapy

Insights From: Catherine T. Frenette, MD, Scripps Green Hospital; Darren S. Sigal, MD, Scripps Green Hospital
Published: Thursday, May 03, 2018



Transcript: 

Darren S. Sigal, MD: Dr. Frenette, what are the criteria for liver resection, and what are the outcomes that we find after laparoscopic liver resection?

Catherine T. Frenette, MD: Liver cancer, in the United States, occurs over 80% in patients who have underlying cirrhosis. Worldwide, there is more hepatitis B–related liver cancer, and a lot of those patients don’t have cirrhosis. Whether or not someone has cirrhosis makes a big difference in terms of whether they’re a resection candidate. As I say to my patients, “Cirrhotic livers don’t like to be operated on.” So, when we’re looking at someone who is potentially a resection candidate, the first question that we ask is, is this liver going to tolerate this? If you’ve got somebody with Child’s A cirrhosis—so, good liver function, a platelet count over 100, which is a surrogate marker for portal hypertension, and a bilirubin of less than 1, which is basically normal—they generally are going to be able to tolerate liver resection, depending on how much of the liver is going to need to be resected to get the cancer out.

After we decide, yes, this liver could potentially tolerate surgery, the patient’s performance status and other medical problems have to be able to tolerate surgery. Then we have the surgeons, and we review it to look at how much liver they are going to take out, and that is where location is everything. If a tumor is right in the middle of the right lobe of the liver, that’s going to be a lot harder to take out than something that’s hanging off the edge of the left lobe. So, those are sort of the criteria that we think about and look at when we’re looking at someone who is a resection candidate. The other thing that we have to think about is, how many lesions are there? The more lesions that you have to resect doesn’t necessarily mean that resection is not an option, it just means that their risk of having disease recurrence is going to be a lot higher. So, we generally shy away from resecting more than just 1 or 2 lesions, just because we know the recurrence rate is more than 70% in those patients.

There is a movement toward laparoscopic liver resection, which is great for the patient. It’s a lot faster recovery, shorter length of stay. It does appear to give equivalent oncologic outcomes and less blood transfusion requirements, which makes sense because a lot of these people do have, again, coagulopathy and portal hypertension that can increase the risk of bleeding. So, those are things that we think about as far as the resection candidates.

Darren S. Sigal, MD: If a patient meets Milan criteria and is a resection candidate, what’s the preference?

Catherine T. Frenette, MD: The Milan criteria, as you know, are the criteria that we use to make a decision as far as listing for liver transplant. So, 1 lesion up to 5 cm or less than 3 lesions all less than 3 cm, no vascular invasion, no extrahepatic spread. However, 1 of the criteria that isn’t often mentioned for liver transplant candidacy for liver cancer patients is that they have to be nonresectable. So, resection is always going to be the preference if it’s possible, partially because we don’t want to expose someone to the immunosuppression of a liver transplant, but also because, honestly, we just don’t have enough livers to transplant everybody. So, we need to really make our choices as far as who we’re going to transplant based on who’s going to benefit the most.

Darren S. Sigal, MD: Can you tell me a little bit about the data related to adjuvant therapy after resection?

Catherine T. Frenette, MD: After resection, sure. I participated in a study, the biggest study on adjuvant therapy that we have. It was called the STORM trial, and it randomized patients after resection or ablation with curative response to sorafenib versus placebo. And the plan was for them to take it for 4 years. The study actually was a negative study. It showed that using sorafenib after resection did not result in any improvement in recurrence rates or survival, so that really showed us that exposing patients to the side effects of adjuvant treatment is really not going to give them a good benefit.

What do you think we should think about as far as recurrent disease? So, after I send someone to resection, we scan them every 3 months for at least 3 years and then usually every 6 months after that because they remain at risk for liver cancer. But when­ I have somebody who has got a recurrence in their liver or extrahepatic, what are our options for those patients?

Darren S. Sigal, MD: When I think about patients with recurrent liver cancer after resection or after transplant, the first consideration I have is, is there an option for local therapy, if possible? If that’s not an option, then the first-line standard of care, based on the SHARP study, is the use of sorafenib. And sorafenib is an oral tyrosine kinase inhibitor that targets multiple pathways—specifically, the VEGFR pathway—and has been shown in a large study of 602 patients randomized to placebo versus sorafenib, to improve overall survival, which is the first randomized study to show an improvement in overall survival in advanced HCC.

Catherine T. Frenette, MD: And I believe even some of those patients in that study were patients who had previously had a resection and now have recurrent disease. I don’t recall the percentage, but I do believe that there were patients in there who met the criteria of that.

Transcript Edited for Clarity 
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Transcript: 

Darren S. Sigal, MD: Dr. Frenette, what are the criteria for liver resection, and what are the outcomes that we find after laparoscopic liver resection?

Catherine T. Frenette, MD: Liver cancer, in the United States, occurs over 80% in patients who have underlying cirrhosis. Worldwide, there is more hepatitis B–related liver cancer, and a lot of those patients don’t have cirrhosis. Whether or not someone has cirrhosis makes a big difference in terms of whether they’re a resection candidate. As I say to my patients, “Cirrhotic livers don’t like to be operated on.” So, when we’re looking at someone who is potentially a resection candidate, the first question that we ask is, is this liver going to tolerate this? If you’ve got somebody with Child’s A cirrhosis—so, good liver function, a platelet count over 100, which is a surrogate marker for portal hypertension, and a bilirubin of less than 1, which is basically normal—they generally are going to be able to tolerate liver resection, depending on how much of the liver is going to need to be resected to get the cancer out.

After we decide, yes, this liver could potentially tolerate surgery, the patient’s performance status and other medical problems have to be able to tolerate surgery. Then we have the surgeons, and we review it to look at how much liver they are going to take out, and that is where location is everything. If a tumor is right in the middle of the right lobe of the liver, that’s going to be a lot harder to take out than something that’s hanging off the edge of the left lobe. So, those are sort of the criteria that we think about and look at when we’re looking at someone who is a resection candidate. The other thing that we have to think about is, how many lesions are there? The more lesions that you have to resect doesn’t necessarily mean that resection is not an option, it just means that their risk of having disease recurrence is going to be a lot higher. So, we generally shy away from resecting more than just 1 or 2 lesions, just because we know the recurrence rate is more than 70% in those patients.

There is a movement toward laparoscopic liver resection, which is great for the patient. It’s a lot faster recovery, shorter length of stay. It does appear to give equivalent oncologic outcomes and less blood transfusion requirements, which makes sense because a lot of these people do have, again, coagulopathy and portal hypertension that can increase the risk of bleeding. So, those are things that we think about as far as the resection candidates.

Darren S. Sigal, MD: If a patient meets Milan criteria and is a resection candidate, what’s the preference?

Catherine T. Frenette, MD: The Milan criteria, as you know, are the criteria that we use to make a decision as far as listing for liver transplant. So, 1 lesion up to 5 cm or less than 3 lesions all less than 3 cm, no vascular invasion, no extrahepatic spread. However, 1 of the criteria that isn’t often mentioned for liver transplant candidacy for liver cancer patients is that they have to be nonresectable. So, resection is always going to be the preference if it’s possible, partially because we don’t want to expose someone to the immunosuppression of a liver transplant, but also because, honestly, we just don’t have enough livers to transplant everybody. So, we need to really make our choices as far as who we’re going to transplant based on who’s going to benefit the most.

Darren S. Sigal, MD: Can you tell me a little bit about the data related to adjuvant therapy after resection?

Catherine T. Frenette, MD: After resection, sure. I participated in a study, the biggest study on adjuvant therapy that we have. It was called the STORM trial, and it randomized patients after resection or ablation with curative response to sorafenib versus placebo. And the plan was for them to take it for 4 years. The study actually was a negative study. It showed that using sorafenib after resection did not result in any improvement in recurrence rates or survival, so that really showed us that exposing patients to the side effects of adjuvant treatment is really not going to give them a good benefit.

What do you think we should think about as far as recurrent disease? So, after I send someone to resection, we scan them every 3 months for at least 3 years and then usually every 6 months after that because they remain at risk for liver cancer. But when­ I have somebody who has got a recurrence in their liver or extrahepatic, what are our options for those patients?

Darren S. Sigal, MD: When I think about patients with recurrent liver cancer after resection or after transplant, the first consideration I have is, is there an option for local therapy, if possible? If that’s not an option, then the first-line standard of care, based on the SHARP study, is the use of sorafenib. And sorafenib is an oral tyrosine kinase inhibitor that targets multiple pathways—specifically, the VEGFR pathway—and has been shown in a large study of 602 patients randomized to placebo versus sorafenib, to improve overall survival, which is the first randomized study to show an improvement in overall survival in advanced HCC.

Catherine T. Frenette, MD: And I believe even some of those patients in that study were patients who had previously had a resection and now have recurrent disease. I don’t recall the percentage, but I do believe that there were patients in there who met the criteria of that.

Transcript Edited for Clarity 
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