Moving the Needle in HCC: International Experts Weigh In - Episode 4
Transcript:Richard S. Finn, MD: We have a patient with chronic liver disease. They’re screened, a tumor is found, and, now, the question is, what is their stage? Staging in oncology and cancer medicine is important for interpreting clinical results from clinical trials, but it’s also important so we can tell patients what to expect—what the prognosis is.
Dr. Bruix, you’re a giant in this space, given your role in developing the BCLC (Barcelona Clinic Liver Cancer) staging system. Could you comment on where BCLC is, where it’s gone, and how it compares to some of the other staging systems?
Jordi Bruix, MD: I am a clinician. When I developed the BCLC staging system, the idea was not to do a boring prognostic assessment. That said, the bigger problem was to decide, who is, let’s say, at an early stage who can benefit, or not, from surgery or transplantation? And who is at the end of the spectrum that everybody could identify?
We had, from the beginning, the idea that some patients are very easy to detect. And then, in the middle, we have this thing that is named unresectable hepatocellular carcinoma. And we have data that showed that some parameters predict a poorer prognosis. We could divide this middle class into 2 classes.
We had the early, the intermediate, the advanced, and the end stage, and we linked this with treatment. Staging is a good, classic connection with the first treatment approach that you may think of. Or, usually, we had arrows. Everybody was very happy. It was simple and clean. But, people have to think.
No single staging system that connects staging with treatment will substitute the need to have a thinking clinician. If you just go by the arrows, you go by mistakes and, there, you have to adapt to comorbidities, age, values, and all these things that make a patient move—despite being early into treatment with systemic therapies or even receiving no treatment because they are too old, too ill, or because of whatever else. You can develop additional parameters to stratify patients according to prognosis, but this may be relevant for trials and not for clinical decision making. So, if this is somebody who might benefit from TACE, he or she will do the same if the AFP is 50 or 5000, probably.
Richard S. Finn, MD: But, a lot of cancer clinicians are used to TNM classification for staging a disease. Liver disease is different. BCLC is different.
Jordi Bruix, MD: The TNM staging system has never been, really, a good predictive outcome in patients with liver cancer, because it just takes into account tumor burden and TNM, which is pathology based. You need to take into account tumor burden, liver function, and health status. The first stage would be the very early stage—single tumor, less than 2 cm in size, preserved liver function, and optimal outcomes with ablation or surgery. The early stage includes single tumors that are symptom-free. There is no limit in size. It is very unlikely that you have a tumor that is 10 cm in size without symptoms but, if they can be ablated, they can be ablated. This was based on the definition of the Milan/Mazzaferro criteria. When this definition of tumor burden is not in place, and the limits are out of this, then you are in “intermediate stage”—again, symptom-free related to cancer. This is important. They have to have liver-only disease, no vascular invasion, no extrahepatic spread, and preserved liver function—meaning compensated liver disease. These are the patients that benefit from chemoembolization.
If you have vascular invasion, extrahepatic spread, chemoembolization is not the option. This belongs to the advanced stage, as there are symptoms. Again, liver function should be preserved. And we have the Child-Pugh score. The Child-Pugh score is informative, but it’s not accurate.
Richard S. Finn, MD: Let’s take a break. So, Child-Pugh is a way to assess liver disease. It takes into account the bilirubin, the international normalized ratio value, albumin, and the presence of encephalopathy or ascites. And those who are Child-Pugh A are better compensated, whereas Child-Pugh C are worse.
Jordi Bruix, MD: They can also have ascites, and they may have had encephalopathy in the past. Or, they may have had bleeding. We know why some Child-Pugh A patients should be considered for transplant. Hepatologists define prognosis not only through the Child-Pugh score, but use MELD (Model for End-Stage Liver Disease), which is useful to predict 3 months’ mortality. But, it does not predict 1-year mortality. This is why the refinement of liver function assessment has to be done not only by Child-Pugh.
Richard S. Finn, MD: But, needless to say, we need to take into account their liver function, their performance status, cancer-related symptoms, and, then, their tumor characteristics. There’s patients who are curable—who have favorable liver function or, we think, fit criteria for transplant. Then, there’s that large group who, I think, are probably most of the patients we see. They are the ones who have vascular invasion or multinodular tumors—Barcelona B, which is intermediate, or C, which is advanced.
Jordi Bruix, MD: I would suggest to avoid the distinction between potentially curative options and palliative, because what you have to select is not to be cured but, rather, what options have the highest likelihood to give patients a life. This is why we have, in the last BCLC version, options that are effective to improve survival. Otherwise, people would say that the best you can get is cure. But, people want to be alive, even if not cured. And this is the concept that has to be stressed.
Richard S. Finn, MD: It’s a complicated disease, and I think that reflects the need for a multidisciplinary approach to properly stage patients and triage patients. There has been, I think, a dominance of the Barcelona staging system, mostly because it’s been well validated in clinical trials. There’s been an effort for new staging systems. Amit, can you comment on some of these?
Amit Singal, MD, MSCS: Yes. The BCLC staging system perfectly balances the complexity of the disease, but, also, is something that’s simple enough for physicians to use on a daily basis. These new staging systems that have come out have started to recognize, or at least have put on paper, something that we’ve known for years—that BCLC B and C are both heterogeneous stages. You’re going to have “early B’s and late B’s” that have different prognoses and different therapies. Similar for C, you have patients that are “early C and late C.”
Richard S. Finn, MD: Stage C.
Amit Singal, MD, MSCS: Stage C, exactly. I think it’s the type of thing where there’s heterogeneity within these groups. This was known when the BCLC was created. It’s known now. But, these staging systems have started to explicitly state so. I think it’s important for physicians who, previously, did not recognize that. I think it can be important for research protocols. Personally, I think it has limited utility in day-to-day practice because, once again, I can draw the BCLC here, but I can’t draw the Hong Kong Liver Cancer staging system. I can’t draw the new Italian staging system (Cancer of the Liver Italian Program). But, once again, they’ve explicitly shown people that BCLC stage B can be broken down into B1, B2, and B3 according to the Italian staging system. And, similarly, the stage C’s can be broken out into several different groups according to the Hong Kong Liver Cancer staging system. I think they’re useful in terms of pointing out something, and I think it can be useful in terms of research protocols and in terms of stratifying patients. I think they have less utility on a day-to-day basis.
Richard S. Finn, MD: So, as things stand, today, for common practice, Barcelona seems to be the backbone for how we approach patients. But, to Dr. Bruix’s point, it needs to be looked at carefully and should be individualized for each patient by the clinical team and the patients.
Amit Singal, MD, MSCS: You need to think beyond the BCLC arrows. You can’t just follow the arrows. Otherwise, there’s no need for a physician.
Richard S. Finn, MD: Sure.
Transcript Edited for Clarity