Key Takeaways in the Treatment of HCC - Episode 1
Richard Finn, MD: Liver cancer is a complex disease. Unlike a lot of malignancies we treat, all of these patients come with 2 comorbidities. One is their underlying liver disease and the other is their malignancy. The association between liver cancer and cirrhosis is very tight. Ninety percent of patients have underlying liver disease, and therefore the outcomes for patients with liver cancer will be dictated by their tumor burden as well as their liver function.
Staging systems that are designed to predict outcomes for patients with liver cancer need to take these 2 factors into account. The Barcelona Clinic Liver Cancer staging system has gravitated toward being 1 of the most commonly used globally. And it breaks patients down from very early stage liver cancer—stage 0—to stages A, B, C, and D, where stage D patients are very advanced and probably ready for hospice care.
The patients with Barcelona stage D are usually in that condition because they have very decompensated liver disease. Child Pugh C [Child Pugh score for cirrhosis mortality] is a way that we commonly assess liver function, taking into account the bilirubin, albumin, INR [international normalized ratio], and whether they have ascites or encephalopathy. Patients with Child Pugh C disease are expected to die from their cirrhosis sooner than from their liver cancer, whereas patients with earlier-stage liver cancer will have better-compensated liver function, as well as smaller tumors.
Then, potentially curable disease would be the patient with stage 0 or A disease. Those are patients who could be resected or undergo radiofrequency ablation for well-compensated liver function and small tumors. The bulk of patients we see present with Barcelona stages B or C. Barcelona stage B is considered intermediate, and often encompasses multifocal tumors in the liver. These patients may have some decompensation in their liver function, but they do not have a tumor growing into their blood vessels or outside of the liver. They also have a good performance status. The Barcelona stage C are those patients who are advanced. These are patients who are appropriate candidates for systemic treatment, assuming that their liver function is adequate. That is to say that they’re not the decompensated patients.
When we assess someone with liver cancer, we ask, “Is this patient going to die of cancer or from cirrhosis?” If it’s going to be the cancer component, what is the best treatment for that patient given their stage, based on their tumor burden, performance status, and other characteristics?
Because liver cancer is complex and there’s an interplay between cirrhosis and cancer, it takes a multidisciplinary team to manage these patients and give them the best opportunity for good outcomes. You involve the oncologist and hepatologists. Liver transplant also plays a very important role in managing these patients and is a curative modality. There are few malignancies for which we do a transplant. We would never transplant a lung for lung cancer, but liver cancer tends to stay in the liver for a while before it spreads outside the liver, or before it develops advanced characteristics like growing into the vasculature. Therefore, liver surgery needs to be involved, as does interventional radiology. Interventional radiology plays a huge role in managing these patients. Patients who have smaller tumors can potentially be cured with radiofrequency ablation if they can’t be operated on. Patients who have multifocal disease in the liver certainly benefit from catheter-based approaches, such as chemoembolization. Increasingly, Y-90 [yttrium-90 radioembolization] is being used for those intermediate patients as well.
When we see a patient, it’s important to get input from everybody. Is this patient going to be curable with surgery? Is the patient within transplant criteria? Transplant criteria are constantly changing, so it behooves us to have a patient assessed at a transplant program with a new diagnosis. Then, is the patient a good candidate for locoregional treatment, or is this a patient who unfortunately might present with advanced disease and need systemic treatment? I would say the majority present with intermediate liver cancer; the patient has liver-confined disease and multifocal tumors. The individual might still be a transplant candidate based on the criteria, or if they can be downstaged. These patients will often get interventional radiology-based treatment—chemoembolization or Y-90—but those are not curative either.
We know that patients who have these procedures will eventually become resistant to them or stage migrate and become advanced. They’ll either develop a tumor outside the liver, or they’ll develop tumor growth into the vasculature, or macrovascular invasion. That doesn’t mean only in the extrahepatic portal vein, but also in the vasculature in the liver. Alternatively, they’ll have a chemoembolization and on their next imaging, they’ll all of a sudden have many new tumors developing, or you can’t completely kill the tumor that you’re targeting. Those are all times to transition to systemic treatment.
With locoregional treatment, usually patients get a treatment and they’re followed and imaged at a regular interval. Often, we do what’s called TACE [transarterial chemoembolization] on demand, so if they have a new tumor, they get another treatment. However, at some point, you start damaging the liver function. Every time you do a TACE, you take away some liver function. At some point, we can’t keep up with the tumor growth or it develops characteristics of advanced disease, and that’s a time to start thinking about systemic treatment.
The oncologist or hepatologist who’s managing that medical component and giving systemic treatment needs to be involved in the conversation, because it’s not readily known that all the new treatments we have available for liver cancer have been proven to extend survival. If a patient continues to get locoregional treatments to the point that their liver function is compromised, they can’t benefit from those treatments. I think we’re looking at solidifying an interaction between locoregional treaters, interventional radiologists, medical oncologists, and hepatologists to help define when we stop TACE and start medical treatment.
Transcript Edited for Clarity