Case 2: A 75-Year-Old With Metastatic HCC


Shifting to a second patient case of metastatic hepatocellular carcinoma, experts consider best diagnostic practices and the initiation of therapy.

Ghassan K. Abou-Alfa, MD:
I’m going to move on to the next case. This is perfect time to talk about systemic therapy for metastatic hepatocellular carcinoma [HCC]. This is a totally different story, with a totally different patient, but 1 who is well represented in the clinic for all of us. The patient is a 75-year-old woman who presented to her primary care physician reporting some abdominal pain and fatigue. As a teaching point, remember the presentation for hepatocellular carcinoma is not particular. It could be subtle symptoms that can happen to any of us. The past medical history of this 75-year-old woman is cirrhosis because of heavy alcohol use. There is also Crohn disease, controlled with infliximab, and a history of variceal bleeding, and it was banded 2 months ago. This is a heavy situation in regard to the cirrhosis with the variceal bleeds banded 2 months ago and added to this the Crohn disease, which is controlled with infliximab. Despite that, the patient performance is ECOG 1, which is great. The CT scan with triphasic of the liver shows a 4.4-cm LI-RADS [Liver Imaging Reporting and Data System] LR-5 hepatic mass in the right lobe, plus metastases in the lung. A Child-Pugh score is A, and the AFP [alpha-fetoprotein] level is 370 ng/mL. With this, there’s no doubt that the initial impression would be critical. Dr Singal, what’s your first impression?

Amit Singal, MD: She’s an older woman who has comorbid diseases. She has portal hypertension with recent variceal bleeding and presents with advanced-stage HCC but good liver function. She’s somebody who falls into the Barcelona Clinic Liver Cancer [BCLC] stage C category, so she would be best treated with systemic therapy. When we fall into the systemic therapy space, 1 of the questions to ask is should you be treated with TKI [tyrosine kinase inhibitor]–based therapy or immune checkpoint inhibitor–based therapy? There are some concerns here.

Ghassan K. Abou-Alfa, MD: Let’s stick to the diagnostic issue. Dr Yarchoan, you and I are keen on getting diagnostic tissue. For this cirrhosis component—let’s say LI-RADS LR-5 or LR-4—would you stick to your biopsy, or do you think differently?

Mark Yarchoan, MD: In this case, everything is strongly pointing to HCC. The AFP is high, the LI-RADS score is LR-5, and the patient has underlying cirrhosis. I don’t think the diagnosis is in doubt. It’s fine to start systemic therapy without a biopsy in this case.

Ghassan K. Abou-Alfa, MD: Are you able to do that at your institution?

Mark Yarchoan, MD: We are.

Ghassan K. Abou-Alfa, MD: The struggle that I have with this is that we don’t want to go in that direction for any point. Can you attest legally that this is HCC based on what you just saw?

Mark Yarchoan, MD: There are guidelines that suggest that you can start systemic therapy with an LR-5 lesion. I fall into the camp where, before starting systemic therapy, it’s never wrong to biopsy. More and more, when we biopsy cases like this, every now and then we’re surprised we end up finding mixed HCC cholangiocarcinoma. I even have a couple of LR-5 lesions that end up being pure cholangiocarcinoma. I fall into the camp that delaying therapy by a week to get a biopsy is never wrong.

Ghassan K. Abou-Alfa, MD: Good. I’m not trying to twist your arm, but I’m glad you bring it up. This is what I know about you, and I give you credit because it’s a concern that the biopsy could be critical, especially now that we go to a third component of it, which probably is yet to be discovered further. Dr Singal, you can help us with the genetic analysis. Would you do it? If you do it, what would be important about it?

Amit Singal, MD: At my center, The University of Texas Southwestern Medical Center, in the setting of cirrhosis, we typically don’t biopsy LR-5 lesions; we don’t do this routinely. We biopsy LR-M lesions, but based on the data we’ve seen, an LR-5 lesion has a 95%, 97% positive predictive value for being HCC. We think that’s fine to treat empirically. We transplant people empirically without a biopsy for LR-5 lesions. It’s probably OK, but if there are any imaging features that would make us unclear about this infiltrated disease—you don’t have classic appearance, there are LR-M lesions, etc—then those are the ones that we biopsy. From a genetic analysis perspective, my feeling is that you can do this, but the number of actionable genetic mutations you find is relatively low in HCC compared with other cancers. Without it changing management, in the cases we do send for biopsy, we’re typically less actionable in terms of genetic mutations. We’re in a nonprecision world for HCC compared with many other cancers.

Ghassan K. Abou-Alfa, MD: I know that’s going to remain a long debate. But intriguingly, and these are the norms that we all agree to, when we talk about surgery, when we talk about transplant, we talk about the cure. Having no touch of the tissue because you’re trying to preserve the potential curability and not transfer the disease to anywhere else, I can understand the new biopsy. We’re going to talk plenty about systemic therapy and the potential adverse events, especially in our patient here. I’d go more for the biopsy.

Transcript edited for clarity.

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