Curative Intent Options in Early-Stage HCC

Transcript:Ghassan K. Abou-Alfa, MD: A patient presents with small disease and really limited, but good liver, what do we do with it?

Amit Singal, MD: If you have either compensated cirrhosis with no signs of portal hypertension, or a non-cirrhotic liver, the first therapy you should consider is surgical resection. As Katie said, it’s not only applicable to hepatitis B [HBV] in terms of having an absence of cirrhosis, but we’re seeing more and more of this with nonalcoholic fatty liver disease [NAFLD]. And actually, the most recent cohort studies suggest that 30% of patients who have NAFLD-related HCC [hepatocellular carcinoma] actually don’t have cirrhosis.

When you see these patients and they have good liver function and a unifocal tumor, we refer those patients for surgical resection if and when possible.

Ghassan K. Abou-Alfa, MD: Fair enough. Katie, let’s take the scenario the other way around. A patient presents with limited disease and a really bad liver; smaller disease but Child-Pugh C. What shall we do with that?

Katie Kelley, MD: We would absolutely work with our multidisciplinary team and evaluate whether they might be a candidate for transplant because that is a therapy that can cure both the underlying liver disease as well as the cancer with outcomes similar to cirrhosis. So we would refer a patient like that for transplant evaluation.

Ghassan K. Abou-Alfa, MD: That’s very important. I also know that TCSF [tumor-cell-derived collagenase stimulatory factor] is quite heavily involved in the criteria for transplant, which we definitely will be guided by to really get the best outcome. And, Farshid, besides surgery and transplant, is there anything else you could think of?

Farshid Dayyani, MD: As was already mentioned, the multidisciplinary management of these patients is paramount. In our tumor board there is a predominance of interventional radiologists [IR] compared to medical oncologists. So local regional treatment is heavily involved in the treatment of these patients: radiofrequency ablation and microwave ablation for smaller tumors.

Ghassan K. Abou-Alfa, MD: Not only can we cure with surgery, but we can also cure with radiofrequency ablation—it’s actual curative intent. This is definitely the nuance of who we can try to cure.

So now, Amit, with regards to transplant, we hear quite a bit about the different criteria, specifically the Milan criteria. Tell us a little more about this as well as the UCSF criteria—what do they mean?

Katie Kelley, MD: The Milan criteria is the traditional criteria that we’ve used for the longest time. These are criteria that were established in Milan, retrospectively, in terms of having the best outcomes from transplant, i.e., the lowest recurrence rates and the best long-term survival. So this was 1 tumor less than 5 centimeters, or 2 to 3 lesions, each less than 3 centimeters, with no vascular invasion or distant metastatic spread.

Ghassan K. Abou-Alfa, MD: So 1 tumor less than 5 centimeters or 3 lesions, each one of them less than 3 centimeters, no vascular invasion and no metastatic disease: these are the Milan criteria. Good.

Amit Singal, MD: Yes. And the University of California San Francisco was one of the centers that expanded our thought process on this. We said, “You know, if the criteria are good, let’s see if we can help more people by making them more eligible for transplant.” They expanded the criteria and what they showed was that these patients have very similar outomces to those within the Milan criteria. For the longest time, this was available on the west coast in addition to Texas and Oklahoma.

Now the landscape of transplant has changed across the United States. What we’ve done is adopted these expanded criteria with the intention of downstaging patients receiving local regional therapy, so that they fall within the Milan criteria, and maintaining that status so that they may receive transplant, and, potentially, great outcomes.

Ghassan K. Abou-Alfa, MD: Katie, I have to admit that I always debate the issue of downstaging. I would love to hear your opinion on that.

Katie Kelley, MD: You know I think it’s really a test of time or a test of tumor biology that we’re employing in parallel with downstaging where we’re making sure to control the tumors we’ve seen through various modalities—usually transcatheter arterial chemoembolization [TACE]. We then make sure that the tumors can achieve the Milan criteria, or the set target remains on the thresholds. At our center I believe that patients during downstaging have to maintain that stage for at least 6 months.

They also have to have an AFP [alpha-fetoprotein] level below a certain threshold. Usually at most centers I believe it’s 500 ng/mL these days. And so during this whole interval of local therapy, going through the transplant evaluation, waiting at least 6 months, waiting for an organ to become available, the biology declares itself in patients with aggressive tumors destine metastasize or be vascular invasive will do so. And unfortunately a transplant isn’t a good choice for those patients; they fall out of the window for transplant.

Conversely, patients with a favorable indolent biology without the capacity to metastasize or suffer vascular invasion will benefit dramatically by local tumor control.

Transcript Edited for Clarity