Richard S. Finn, MD: Alpha-fetoprotein [AFP] has been around for a long time, right? How do you approach the use of AFP in diagnosing patients with liver cancer?

Pierre Gholam, MD: As an AFP enthusiast, we have had a love-hate relationship with AFP in the hepatology field. AFP was, at first, an established end point, a requisite end point in our surveillance strategies endorsed by all societies. Circa 2010 we realized that AFP by itself does not add much in terms of sensitivity and specificity. In fact, the US hepatology society, AASLD [American Association for the Study of Liver Diseases], dropped it from its guidelines for a while. Clearly, AFP has now been established to be of value in terms of determining prognosis.

It is not a good measure of or means of establishing a diagnosis. We would all agree on that. In fact, if you look at various clinical trials in first- and second-line settings, you can tell that the cutoff for AFP is useful in delineating response to therapy in some patients, but it could also could potentially, to some extent, predict the degree to which people might benefit from therapy. If you ask me about whether I use AFP in my surveillance algorithm for patients with HCC [hepatocellular carcinoma], I would say that I absolutely do in every patient in combination, of course, with imaging. I don’t use dynamic imaging for surveillance, but clearly the limitations of AFP have to be factored into this.

Richard S. Finn, MD: For the audience, we need to distinguish between screening and diagnosis, and you touched on that toward the end. Because of the complexity of underlying liver disease and tumor burden, outcomes and studies have shown that the patients with cancer who do the best are those who have better-preserved liver function. Ideally, patients who have chronic liver disease are screened on a regular basis. To your point, the guidelines recommend an ultrasound every 6 months, and whether you add AFP to that is where your desire is to incorporate it into screening vs diagnosis. You touched on the fact that AFP doesn’t necessary play a role in diagnosis; that’s dynamic imaging. When you make the diagnosis of liver cancer, how do you assess liver function? How do you assess whether this patient is a good candidate for aggressive treatments?

Pierre Gholam, MD: There are tried-and-true methods of assessing “liver function.” These were mainly derived in response to the need for patients with advanced liver disease to receive surgery. Surgeons obviously don’t like taking patients to the OR [operating room] and not having a good outcome. We had to figure out a way to understand who might fare well with surgery, and by extension, this turned out to be a pretty good method to assess survival at a finite period of time. The tried-and-true method for over 4 or 5 decades is the Child-Pugh-Turcotte score, which is a combination of 3 objective and 2 subjective criteria that you tabulate. The subjective criteria are ascites and hepatic encephalopathy. Your objective criteria are PT [prothrombin time]/INR [international normalized ratio], albumin, and bilirubin. You add those up, and if you exceed 6 points, then you have Child-Pugh B. That puts you at a reduced likelihood of survival at 1 year, although your survival is still expected to be around 60% to 70%. If you exceed 9 points, then you have Child-Pugh C cirrhosis. That’s someone whose life expectancy at 1 year probably does not exceed 50% to 60% in the modern era. That’s 1 way to do it. It’s not a perfect way, but it’s certainly a helpful way to assess liver function.

Richard S. Finn, MD: That has been incorporated into the Barcelona staging system, right? The BCLC [Barcelona Clinic Liver Cancer] has gravitated to be the main staging algorithm for how we conduct clinical studies and therefore how we can relate to patients in the clinic. To your point, if we have a patient who is Child-Pugh C, they are going to die of liver disease before they die of cancer in general, right?

Pierre Gholam, MD: Absolutely.

Richard S. Finn, MD: As we will discuss, as we have more active drugs, there are probably some patients who have decompensated liver disease from a large tumor burden. Perhaps if we improve their tumor burden safely, then they might improve their liver function. In general, when patients are cerotic, that’s a competing risk for death. That’s why staging systems that we use, like TNM [tumor node metastasis] and other malignancies, don’t carry enough weight in the liver cancer space because they ignore the competing risk for outcomes, which is liver disease.

Most studies have concentrated on patients who are Child-Pugh A. The Child-Pugh B group is very heterogeneous. We’ll talk later about how we approach those patients. In treating them with systemic medications, you generally see that they’re excluded from clinical trials.

Transcript Edited for Clarity