Systemic Therapy for HCC: A Rapidly Evolving Landscape - Episode 3
A debate regarding the current role of biopsy to confirm a diagnosis of early-stage hepatocellular carcinoma.
Amit Singal, MD: Tony, I said that I don’t biopsy for confirmatory diagnosis if somebody has definite HCC [hepatocellular carcinoma]. But once again, these imaging features have been the best and the worst thing that has ever happened in the field of HCC. I see some of my colleagues here shaking their heads. I think they’re shaking it on the worst side of HCC, more than the best side of HCC—in the sense of you will hear for the next hour-plus—because we haven’t had as many advances in the field of HCC as any of us would like. We’ve seen tremendous, targeted advances in other cancers, but in HCC we continue to be dumbfounded, and our clinical advances tend to be much slower with many more negative trials than we should have had. It’s because of our lack of tissue to facilitate research. I’m personally against diagnostic biopsies to confirm a diagnosis. Academic centers and people who do research I think research biopsies to facilitate a better understanding of HCC, particularly as part of clinical trials. Something we need to be more aggressive with in terms of facilitating an understanding of tumor biology and targets and prognosis.
Tanios S. Bekaii-Saab, MD, FACP: I see. Arndt, any thoughts?
Arndt Vogel, MD: Overall, I agree with what Amit said, but I’m not sure whether we should not biopsy in HCC for a couple of reasons. First, we’re all experts, and I completely agree with you. If you have a perfect CT patient at risk with cirrhosis and an expert radiologist, you can make the diagnosis with very high accuracy. This isn’t what we see in the community. The majority of our CTs are not usable. We have to repeat many of them. Many of our colleagues in the community aren’t really expert in diagnosing HCC. Overall, I’m not so convinced that we’re really sensitive enough to clearly distinguish HCC and pharyngeal carcinoma, specifically the mixed-type tumor. We’ve seen that since we started sequencing, it took a while.
We’ve seen a lot of fusions—FGFR2 fusions, for example—in mixed-type tumors. Personally, the majority we have we would have met because they were patients with cirrhosis, at risk. Because we always biopsy, we identified them as mixed type, pharyngeal, on your hepatocellular carcinoma, can be identified confusion. Therefore, there are a couple of studies coming out… They’re really careful in the United Kingdom; biopsy is required to prescribe throughout medicinal. They had the chance to compare biopsy and radiological criteria. It’s not as perfect as we think. From our own experience, in 5% to 10% of patients, you misdiagnose, or you make the wrong diagnosis. We’re talking about precision medicine, and that’s not accepted anymore. Therefore, we should be more open, keeping in mind that not only experts and expert CTs are performed. There might be some patients for whom we should be cautious. Liver transplantation is something we of course need to discuss. But overall, yes.
Amit Singal, MD: It’s a great point. I’m speaking from an idealistic perspective in the sense of getting a high-quality CT or high-quality MRI. Your point is well taken that not everyone has access to top-tier imaging or top-tier radiologists. I consider myself fortunate that we do have those at our institution. Many of many of us do. I don’t think we should also undersell what’s available in the community. You do see top-tier imagers and imaging modalities. Your point is well taken that if you don’t believe you have access to that, it’s worth accessing some high-quality imaging and radiologists or considering biopsy in those confirmatory cases. Your second point about mixed tumors is also extremely important. I agree with you that we’re seeing more of these. I don’t know if we’re seeing more of these because there’s shifting in epidemiology or because we’re looking. If you don’t look, you’d never find anything. I’ve been surprised at times when we’ve done these biopsies at how many people do have mixed tumors. We’re potentially treating those people differently. In our center, mixed tumors are the biggest question. I don’t think we necessarily even know how to treat mixed tumors. If you’re going to get a mixed tumor, and you’re like, “I’m going to do the same thing,” then why take a look under the hood? It’s the type of thing for which a biopsy is a small portion. I don’t think you’re able to say on biopsy, is this majority cholangiocarcinoma, majority HCC? Basing your decision sometimes on that biopsy can also be difficult. But your points will take in that if you don’t look, you’re not going to find some of these mutations that can be actionable. I have to say, in our experience, the actionable mutations tend to be relatively rare. When you look at this from a population perspective, at least based on the data I’ve seen—and it may be evolving—the risk-benefit ratio justifies biopsy in all.
Tanios S. Bekaii-Saab, MD, FACP: This is a great discussion. It’s a moving target, but I agree, we’re moving into a world where we do need to enhance our likelihood of finding targets to go after. Mark, I’m going to give you the last word before we move on to the next subject.
Mark Yarchoan, MD: It’s great that we have the freedom to start therapy based on a radiographic diagnosis, but I don’t think it’s ever wrong to biopsy a patient with advanced-stage disease. Five years ago, the risk of getting the wrong diagnosis was not that big because sorafenib prolongs life by 3 months. Gemcitabine-cisplatin prolongs life by a couple of months. The risk benefit may not have been there. Biopsies are painful. They have complications, but we’re entering a different era. We’ve all seen patients who are cirrhotic, who have classic risk factors, who have a LI-RADS [Liver Imaging Reporting and Data System] 5 scan—and that’s an excellent-quality scan—who have an AFP [alpha fetoprotein] of 5000 ng/mL. You biopsy them, and they’re a mixed subtype with an FGFR mutation or fusion, and they respond nicely to targeted therapy. We’ve all seen this if we do this all day. I’m of the opinion that it’s fine to start therapy when you have a radiographic diagnosis. If there’s something about the tumor that makes you a little uncomfortable—a slightly high CA [cancer antigen] 19-9, for example—then I’m on the side that it’s worth biopsying.
Transcript Edited for Clarity