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Diagnosing HCC: When a Biopsy is Needed

Panelists: Richard S. Finn, MD, Geffen School of Medicine; Jordi Bruix, MD, Hospital Clinic University of Barcelona; Amit Singal, MD, MSCS, UT Southwestern Medical Center; Richard H. Marshall, MD, University Medical Center New Orleans; Arndt Vogel, MD, PhD, Hanover Medical School
Published: Monday, Jul 10, 2017



Transcript:

Richard S. Finn, MD:
What’s really interesting about liver cancer, versus other malignancies we treat, is that it’s really 2 diseases. It’s chronic liver disease, as we’ve heard, and, then, it’s a cancer anatomical problem. Given that association with underlying liver disease, and given that the only way to cure the disease is really with a surgical approach—either transplant or resection—I think a lot of opinion is that patients are best managed in a multidisciplinary center. Dr. Marshall, can you comment on what a multidisciplinary program looks like at an academic center? Does that exist outside of academia?

Richard H. Marshall, MD: This is something that’s very easy to overlook for many physicians. It’s important to know that patients who are treated through multidisciplinary approaches often have better outcomes with increased survivals. They’re often offered more therapies than those patients treated outside of a multidisciplinary setting.

Ideally, the multidisciplinary setting includes all physicians and supporting personnel who will take care of the patient. We can involve medical oncologists, surgical oncologists, and hepatobiliary surgeons. We need hepatologists involved in this care. Primary care physicians are crucial in managing other issues that come up with these patients, as well as interventional radiologists. And don’t forget the diagnostic radiologists who can often help make these diagnoses and point out other things about these tumors that may make them higher risk, such as portal vein invasion, extrahepatic disease, and things like that.

Richard S. Finn, MD: In an academic center, that might be easy. But, in the community, how should doctors try to interact?

Richard H. Marshall, MD: What we see, in the United States, is that community physicians often don’t have the support that these larger academic centers have. And so, referral pathways are very important in these instances and with a lot of other diseases. Communication is crucial in these settings—a pathway to refer patients to a larger center in which the referring physicians can pass along information or receive information. I can add, they may still act as that patient’s primary care physician. A need to stay in the loop with what’s going on with these patients is very important.

Richard S. Finn, MD: Yes, I think those are good points. Ultimately, given that any one physician in the United States, or even globally, might not see a lot of liver cancer, if you’re an oncologist or gastrointestinal doctor, referring often to a larger center that can provide access to people who only concentrate in this disease is probably best for patients, if it can happen.

Richard H. Marshall, MD: Absolutely.

Richard S. Finn, MD: We spent a lot of time talking about screening for liver cancer to find nodules, early. I think clinicians often think, “A nodule? I need a biopsy.” Do we always need to do a biopsy to make the diagnosis of liver cancer?

Richard H. Marshall, MD: Well, we’ve seen a large shift in this. Previously, before the advent of the LI-RADS (Liver Imaging Reporting and Data) system, interventional radiologists were performing a lot of biopsies to make these diagnoses. Now, we are able to make a diagnosis of hepatocellular carcinoma based on cross-sectional imaging. Patients will go from a screening study, which is usually an ultrasound with or without an AFP, to a contrast enhanced study, whether it’s a CAT scan, a triple-phase liver CT, or a dynamic MRI. A contrast-enhanced ultrasound is also useful in that area.

When we do these types of imaging, we are really looking at the blood flow in the liver. And so, we inject some contrast into a vein, and we watch it over time as it flows through the liver to identify a hypervascular tumor and see something within the liver that’s perfused differently than normal liver parenchyma. Based on some characteristics of these tumors, we can identify, definitively, that a patient has HCC. There are other categories in which we think a patient is at very high risk for HCC, based on some tumor characteristics, but it’s not definitively diagnostic. In that situation, yes, we do pursue biopsy in some instances. But the role of biopsy has really decreased, lately.

Jordi Bruix, MD: The criteria that are diagnostic, LI-RADS, are exactly the same criteria that were developed by the AASLD (American Association for the Study of Liver Diseases) and others. “LI-RADS score 4 or 5—OK.” You have a score of 2 or 3. The fact that you have low probability does not mean that this is not relevant for the individual. So, it’s not about going to the casino. If you have, let’s say, a LI-RADS score of 2, and you have a 10% probability, you will never tell a patient, “Oh, don’t worry, you have a low likelihood to have cancer—just a 1 in 10 risk.” He or she will say, “I’m sorry, 1 in 10? Biopsy.”

The stratification, according to risk, is good for betting money, but not for disease. And so, I think this is something that has to be clarified. Otherwise, we will see patients that could have been diagnosed, early, of liver cancer, but are delayed until they reach 4 or 5 criteria with LI-RADS, and this will be a disservice.

Richard H. Marshall, MD: I agree with you. These are the subtleties that come up that are often best treated in multidisciplinary settings—patients who may need to continue screening, who are considered to be very high risk, or who should undergo additional surveillance versus biopsy. These patients don’t fit classification systems, and they need that individual care.

Richard S. Finn, MD: Yes, of course. I think that Dr. Bruix’s point is well taken. If you have a LI-RADS score of 2, it doesn’t mean you go away and you’re never seen again. You just stay in the system and continue imaging.

Jordi Bruix, MD: This is why it’s characteristic or it’s undetermined. And, if this is the case, the only way to go is to take a biopsy if you want to treat. If you do not want to do treatment, then you can do whatever you want.

Richard S. Finn, MD: I think we’ll come back to that when we talk about staging. Liver cancer, as we’ve heard, in the correct setting—chronic liver disease, a hypervascular tumor—we can say with confidence is liver cancer without a biopsy. A lot of cancer medicine is moving towards biopsy-driven, biology-driven diagnoses and treatment. By not doing biopsies, have we somewhat shot ourselves in the foot?

Amit Singal, MD, MSCS: I think that’s an interesting question. The goal of where we want to take medicine is, really, precision medicine—tailoring therapies to individual patients. Most HCC trials, to date, have been in all-comers. It hasn’t really been biology-driven. We just had our first HCC trial that was really biomarker driven—the tivantinib study that was for c-MET-positive patients. Unfortunately, the results were negative, but it was a study that went that direction. In my opinion, I think this is really where we should aim to go.

In terms of their goal of biopsy to do this, I think that, first, if you don’t have a trial that is biomarker-driven, I don’t think we should be doing routine biopsies on patients. And then, in terms of your question of, have we shot ourselves in the foot, I think you’re probably right—we have less of an understanding than we probably should. That being said, I don’t think that biopsies should be routinely done in all centers. I think it either needs to be done on a research protocol or as part of clinical trials. And with more and more clinical trials now mandating a biopsy, I think we are going to learn more about this over time.

Richard H. Marshall, MD: I agree with Dr. Singal. I think we need to use biopsy when it’s going to affect therapies. As of right now, we’re starting to see, as you mentioned, an expansion of our therapies. Hopefully, we’ll see an increase in the role in biopsy for that in the future.

Transcript Edited for Clarity

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Transcript:

Richard S. Finn, MD:
What’s really interesting about liver cancer, versus other malignancies we treat, is that it’s really 2 diseases. It’s chronic liver disease, as we’ve heard, and, then, it’s a cancer anatomical problem. Given that association with underlying liver disease, and given that the only way to cure the disease is really with a surgical approach—either transplant or resection—I think a lot of opinion is that patients are best managed in a multidisciplinary center. Dr. Marshall, can you comment on what a multidisciplinary program looks like at an academic center? Does that exist outside of academia?

Richard H. Marshall, MD: This is something that’s very easy to overlook for many physicians. It’s important to know that patients who are treated through multidisciplinary approaches often have better outcomes with increased survivals. They’re often offered more therapies than those patients treated outside of a multidisciplinary setting.

Ideally, the multidisciplinary setting includes all physicians and supporting personnel who will take care of the patient. We can involve medical oncologists, surgical oncologists, and hepatobiliary surgeons. We need hepatologists involved in this care. Primary care physicians are crucial in managing other issues that come up with these patients, as well as interventional radiologists. And don’t forget the diagnostic radiologists who can often help make these diagnoses and point out other things about these tumors that may make them higher risk, such as portal vein invasion, extrahepatic disease, and things like that.

Richard S. Finn, MD: In an academic center, that might be easy. But, in the community, how should doctors try to interact?

Richard H. Marshall, MD: What we see, in the United States, is that community physicians often don’t have the support that these larger academic centers have. And so, referral pathways are very important in these instances and with a lot of other diseases. Communication is crucial in these settings—a pathway to refer patients to a larger center in which the referring physicians can pass along information or receive information. I can add, they may still act as that patient’s primary care physician. A need to stay in the loop with what’s going on with these patients is very important.

Richard S. Finn, MD: Yes, I think those are good points. Ultimately, given that any one physician in the United States, or even globally, might not see a lot of liver cancer, if you’re an oncologist or gastrointestinal doctor, referring often to a larger center that can provide access to people who only concentrate in this disease is probably best for patients, if it can happen.

Richard H. Marshall, MD: Absolutely.

Richard S. Finn, MD: We spent a lot of time talking about screening for liver cancer to find nodules, early. I think clinicians often think, “A nodule? I need a biopsy.” Do we always need to do a biopsy to make the diagnosis of liver cancer?

Richard H. Marshall, MD: Well, we’ve seen a large shift in this. Previously, before the advent of the LI-RADS (Liver Imaging Reporting and Data) system, interventional radiologists were performing a lot of biopsies to make these diagnoses. Now, we are able to make a diagnosis of hepatocellular carcinoma based on cross-sectional imaging. Patients will go from a screening study, which is usually an ultrasound with or without an AFP, to a contrast enhanced study, whether it’s a CAT scan, a triple-phase liver CT, or a dynamic MRI. A contrast-enhanced ultrasound is also useful in that area.

When we do these types of imaging, we are really looking at the blood flow in the liver. And so, we inject some contrast into a vein, and we watch it over time as it flows through the liver to identify a hypervascular tumor and see something within the liver that’s perfused differently than normal liver parenchyma. Based on some characteristics of these tumors, we can identify, definitively, that a patient has HCC. There are other categories in which we think a patient is at very high risk for HCC, based on some tumor characteristics, but it’s not definitively diagnostic. In that situation, yes, we do pursue biopsy in some instances. But the role of biopsy has really decreased, lately.

Jordi Bruix, MD: The criteria that are diagnostic, LI-RADS, are exactly the same criteria that were developed by the AASLD (American Association for the Study of Liver Diseases) and others. “LI-RADS score 4 or 5—OK.” You have a score of 2 or 3. The fact that you have low probability does not mean that this is not relevant for the individual. So, it’s not about going to the casino. If you have, let’s say, a LI-RADS score of 2, and you have a 10% probability, you will never tell a patient, “Oh, don’t worry, you have a low likelihood to have cancer—just a 1 in 10 risk.” He or she will say, “I’m sorry, 1 in 10? Biopsy.”

The stratification, according to risk, is good for betting money, but not for disease. And so, I think this is something that has to be clarified. Otherwise, we will see patients that could have been diagnosed, early, of liver cancer, but are delayed until they reach 4 or 5 criteria with LI-RADS, and this will be a disservice.

Richard H. Marshall, MD: I agree with you. These are the subtleties that come up that are often best treated in multidisciplinary settings—patients who may need to continue screening, who are considered to be very high risk, or who should undergo additional surveillance versus biopsy. These patients don’t fit classification systems, and they need that individual care.

Richard S. Finn, MD: Yes, of course. I think that Dr. Bruix’s point is well taken. If you have a LI-RADS score of 2, it doesn’t mean you go away and you’re never seen again. You just stay in the system and continue imaging.

Jordi Bruix, MD: This is why it’s characteristic or it’s undetermined. And, if this is the case, the only way to go is to take a biopsy if you want to treat. If you do not want to do treatment, then you can do whatever you want.

Richard S. Finn, MD: I think we’ll come back to that when we talk about staging. Liver cancer, as we’ve heard, in the correct setting—chronic liver disease, a hypervascular tumor—we can say with confidence is liver cancer without a biopsy. A lot of cancer medicine is moving towards biopsy-driven, biology-driven diagnoses and treatment. By not doing biopsies, have we somewhat shot ourselves in the foot?

Amit Singal, MD, MSCS: I think that’s an interesting question. The goal of where we want to take medicine is, really, precision medicine—tailoring therapies to individual patients. Most HCC trials, to date, have been in all-comers. It hasn’t really been biology-driven. We just had our first HCC trial that was really biomarker driven—the tivantinib study that was for c-MET-positive patients. Unfortunately, the results were negative, but it was a study that went that direction. In my opinion, I think this is really where we should aim to go.

In terms of their goal of biopsy to do this, I think that, first, if you don’t have a trial that is biomarker-driven, I don’t think we should be doing routine biopsies on patients. And then, in terms of your question of, have we shot ourselves in the foot, I think you’re probably right—we have less of an understanding than we probably should. That being said, I don’t think that biopsies should be routinely done in all centers. I think it either needs to be done on a research protocol or as part of clinical trials. And with more and more clinical trials now mandating a biopsy, I think we are going to learn more about this over time.

Richard H. Marshall, MD: I agree with Dr. Singal. I think we need to use biopsy when it’s going to affect therapies. As of right now, we’re starting to see, as you mentioned, an expansion of our therapies. Hopefully, we’ll see an increase in the role in biopsy for that in the future.

Transcript Edited for Clarity
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