A review of prognostic factors and the importance of understanding underlying liver disease to help stage and treat patients with hepatocellular carcinoma.
Richard S. Finn, MD: When we think about patients with liver cancer, we need to stage them to understand how best to treat them. The tumor, node, metastases, or TNM, formula that we use in most other malignancies fails to adequately prognosticate outcomes for advanced liver cancer, or all liver cancer, I should say. The reason it fails is because it misses a key prognostic factor in patients with advanced liver cancer, which is the extent of their underlying liver disease: ie, their cirrhosis. Staging systems that take into account not only tumor characteristics but also liver physiology characteristics are most accurate.
In the academic community and now in community practice, the Barcelona Clinic Liver Cancer [BCLC] staging system has become a backbone for how we approach patients. The BCLC divides patients into 5 stages from stage 0, which is very early stage, to stage D, which is advanced and decompensated patients who should receive supportive care. In the middle, we have patients who are stage A, B, and C.
Patients who are stage A are those who could potentially be cured with transplant, but they probably are not resection candidates because of their underlying liver disease. One of the main determinants for whether a patient could have surgical resection is thrombocytopenia because this reflects the patient's degree of portal hypertension. There are many patients out there in the primary care community who run platelet counts of 130,000/mcL, 120,000/mcL, which is not dangerous, but it is clearly abnormal, and it is often one of the signs of undiagnosed liver disease. When we are talking about patients who need resection, we are talking about platelet counts that are under 100,000/mcL, which would indicate significant portal hypertension. For patients who cannot be cured with surgical approaches, we clearly have ways to treat these patients.
Many patients will present with BCLC stage B, which is intermediate liver cancer. These patients have well-compensated liver disease, but they typically have multifocal tumors in the liver, which are not amenable to resection for various reasons. Therefore, locoregional treatments have been the backbone, such as the chemoembolization procedures, TACE [transarterial chemoembolization], which has clearly been shown to improve survival.
For patients who have advanced disease or BCLC stage C, we have relied on systemic treatments. There are a few nuances to keep in mind. First, patients can have advanced liver cancer without having disease outside their liver. Clearly, if the patient has extrahepatic spread or metastases, they are advanced, BCLC stage C.
However, patients can have large tumors in the liver that are causing cancer-related symptoms or multifocal tumors that are not amenable to chemoembolization. Patients who have tumors invading the vasculature of the liver do not receive optimal outcomes with procedures such as TACE. When we see on a report the term macrovascular invasion, or MVI, this is indicative of a tumor growing into the portal vasculature, which is an indication of advanced disease.
Some patients who have intermediate disease can still be considered for transplant, and one of the take-home messages here is that the criteria for transplant are always changing. We are able to take patients who have larger tumors and downstage them with locoregional treatments. Therefore, if possible, patients should be assessed at a liver transplant center or certainly a place that has a high surgical volume. These places also often have multidisciplinary tumor boards, and these tumor boards help facilitate optimal care because this is a complex disease. It is really 2 diseases: liver disease and malignancy, so it involves several areas of expertise including transplant surgery and hepatobiliary surgery. These are sometimes the same group, but they are often separated. It also includes interventional radiology, which does things like ablations, which are percutaneous, or vascular approaches such as TACE or even radioembolization, as well as hepatology and GI [gastroenterology], and physicians such as myself in medical oncology.
Transcript edited for clarity.