Systemic Therapy for HCC: A Rapidly Evolving Landscape - Episode 1
A brief overview of criteria and tools used to assess, and risk stratify patients with early stage hepatocellular carcinoma.
Tanios S.Bekaii-Saab, MD, FACP: Hello and welcome to this OncLive® Peer Exchange titled, “Systemic Therapy for Hepatocellular Carcinoma: A Rapidly Evolving Landscape.” My name is Tony Bekaii-Saab. Joining me today in this discussion are my esteemed colleagues and super experts in the field: Edward Kim, MD; Anjana Pillai, MD; Rachna Shroff, MD; Amit Singal, MD; Arndt Vogel, MD; and Marc Yarchoan, MD. Today we are going to discuss a number of topics pertaining to the use of systemic therapy in advanced hepatocellular carcinoma [HCC]. We will discuss the latest research in the field, and the impact of recent clinical trials on making decisions around treatment selection, which has become quite complex. But excitingly, we’re moving the field forward. Let’s get started on the first topic, and this would be on early stage hepatocellular carcinoma. I want to start with, Anjana. We are trying to understand, as this field is moving more and more toward early detection, trying to bring patients earlier into a more curable setting. What is happening in that in that setting?
Anjana Pillai, MD: Thank you. First as a background, we can all agree that surveillance is important, especially in patients with advanced liver disease and cirrhosis. That has been set aside. The second thing is that guidelines do vary but recommend using abdominal ultrasound with or without AFP [alpha-fetoprotein] every 6 months. The bigger question, what you’re asking, is how do we risk stratify these patients in the meantime? Who is at highest risk versus lowest? The AASLD [American Association for the Study of Liver Disease] recommends surveillance in patients with cirrhosis only. But EASL [European Association for the Study of the Liver], the European society, also recommends it for advanced fibrosis, or F3. The question is what tools should we use to identify these patients who are highest risk? As hepatologists, I think we have different tools we can use. There are scoring systems like FIB-4 [Fibrosis-4], there’s transient elastography, there are HCC risk calculators for viral hepatitis. All of those things can help us identify, in some sense, who are the patients at highest risk, as well. The other aspect is, what modality should we use? As I stated, ultrasound is what the guidelines recommend, but recent studies have shown about 1 in 5 are inadequate, and ultrasound alone is only sensitive in about 50% in identifying early lesions, like T1 and T2 lesions, and adding AFP increases it to somewhere around 60%, but it’s not ideal. The question is, can we use things like MRI or abbreviated MRI in higher-risk patients? Those are the tools that we have right now.
Tanios S.Bekaii-Saab, MD, FACP: Yes, where are we going with all this? The Mayo Clinic has been quite involved with some of that, and you and others as well. Where are we moving into the world of molecular testing and circulating tumor DNA, methylating DNA markers? Do you see this ultimately changing the world of early detection?
Anjana Pillai, MD: I think so, it’s very important. We’ve all been waiting for these liquid biomarkers, so to speak this Holy Grail, to help us identify these subsets of patients. There are lots of studies out there; the issue is many are low quality in evidence, and so they’re not implemented in clinical practice. I think the HCC early detection strategy at the NIH [National Institutes of Health] Early Detection Research Network, they created these huge biorepositories and databases to look at this specific question. These ongoing phase 2 trials will help us answer that. I certainly think that is the future, and also the evolution of radiomics, extracting imaging data and clinical data to predict outcomes, and ideally with a biomarker, are even more important. I think it’s happening. It’s just not readily available right now.
Tanios S.Bekaii-Saab, MD, FACP: What are some of the biggest challenges for early detection? Those patients have to be followed through for long periods, at least those with liver disease who are at risk. In your clinic, what are the biggest challenges and the complexities for increasing our level of efficiency in early detection?
Anjana Pillai, MD: One is referral patterns, making sure these patients with cirrhosis are referred to a gastroenterologist or hepatologist, to make sure they do undergo surveillance. Amit has done a lot of work on this, making sure there’s provider education, patient education. There are limiting factors, again, of using an ultrasound, including patients who are obese, who have ascites; ultrasound is operator dependent. What do you do with inadequate studies? Do you follow up with cross sectional imaging? Do you repeat the ultrasound again, whether it’s 3 months or 6 months?There’s a lot of disparity in how people use surveillance right now. Those are areas that need to evolve a little better. Then there are some insurance hurdles; I would love to get an MRI on everyone, but that’s not going to fly. And what’s considered cost effective? Those are real problems, and again, effective biomarkers; using AFP over time, longitudinally, the only biomarker we readily commonly use, is great. But it doesn’t detect HCC in 30%, 40% of patients. Using some of these other biomarkers should help in detecting, early surveillance.
Tanios S.Bekaii-Saab, MD, FACP: Our hope is moving into an easier world of biomarkers that are more accurate in the field. Amit, you were going to say something.
Amit Singal, MD: Yes, Anjana brought up a great point and it’s an important point. Right now, when we take a look at the at-risk cohort, only 1 in 4 people are getting surveillance per guidelines. It’s important, because we talk about all of the nuances of what we can do and what we should do. It’s important to remember that the majority of patients right now are not getting any surveillance. We talk about, should we do an ultrasound, should we do an MRI? Once again, these are nice debates to have, but the key thing is to do something. As Anjana was saying, right now, surveillance is ultrasound-based, which can be quite difficult to do. There are the provider barriers. We’ve conducted some survey studies among providers. These are pressures we all face, we’re being asked to do more and more in a short period of time. It’s not only with the patient, but it’s all the Epic [health record system]-related stuff that we have to do as well during that same period. There are also patient-reported barriers in terms of getting that ultrasound done. There are financial barriers, transportation barriers, logistical barriers, and those are part of the reason this isn’t being done in the majority of patients. The nice thing about biomarkers is not just increasing sensitivity, and improving test accuracy, but making this super easy on patients, because they see that patient in the clinic, and they get that biomarker done the same day. It can dramatically improve effectiveness of early detection in clinical practice.
Transcript Edited for Clarity