2021: The Year of Advances in Unresectable HCC? - Episode 3
Examining individual patient assessment for using TACE (transarterial chemoembolization) in unresectable BCLC (Barcelona Clinic Liver Cancer) stage B hepatocellular carcinoma and the health care team involved.
Amit Singal, MD, MS: When we think of somebody who has intermediate-stage HCC [hepatocellular carcinoma] that is unresectable, we’re left with a host of treatment options. Chemoembolization, or locoregional therapy in general, has been the standard approach to patients with intermediate-stage HCC, supported by multiple cohort studies, small RCTs [randomized controlled trials], and most notably a systematic review that showed improved survival compared to no treatment when we consider the benefit of chemoembolization.
One thing we have to consider when we look at that evidence base is that most patients who have been included in those trials with chemoembolization had fairly limited tumor burden. Over time, we’ve seen expansion of chemoembolization to patients with larger tumors, multifocal, bilobar tumors, in which those patients were not included in our historic evidence base. It doesn’t mean that chemoembolization, radioembolization, or other locoregional therapies can’t be of benefit, but when we take a look at our evidence base that supports this clinical practice, many of those patients weren’t truly included in those larger trials.
When I think of our approach to locoregional therapy in these patients, it goes back to the same paradigm of benefits and harm. When we think of these patients who have larger tumor burden, for example, thinking about some of the paradigms that have been put out there—up-to-7 criteria [sum of the size of the largest tumor and total number of tumors] or beyond the 6 and 12 criteria, so beyond 12—whatever criteria you use, these patients with larger multifocal tumors, we have to think are we truly helping our patients when we deliver locoregional therapy to these patients? That concept of helping our patients is not only based on the ability to induce responses or improve progression-free survival, but also the risk of liver injury. Even if you induce a response in that tumor, you may be offsetting that benefit from a tumor perspective by inducing liver injury in the background cirrhosis. We’ve clearly seen these patients who have post-embolization syndrome or hepatic dysfunction after locoregional therapy, who are likely harmed and have shorter survival after giving these nonselective chemoembolization or radioembolization approaches. I think that’s why when we’ve seen the way that locoregional therapy is delivered in clinical practice, we’ve seen advances where we’ve gone to more and more selective approaches to minimize that risk of liver injury when we’re doing locoregional therapy.
When we think of a patient who is eligible for chemoembolization, the optimal patient is somebody who has limited tumor burden in the setting of good liver function, so typically a patient with a Child-Pugh A score and somebody with typically good performance status [PS]. These are the patients who were included in our historic evidence base for chemoembolization and the ideal patient for chemoembolization when we apply this in clinical practice.
Unfortunately, those ideal patients make up a minority of the patients that we see in our routine every-day clinical practice. We see an expansion of locoregional therapies being applied to patients who have some degree of underlying hepatic dysfunction, some impaired performance status, and perhaps larger tumors than we would like. I think many of us do apply limits in terms of when we would not do chemoembolization or other locoregional therapies. For example, in our clinical practice, we will do locoregional therapies in somebody who has Child-Pugh B7, Child-Pugh B8 disease. We’re a little more reluctant to apply this in a patient with Child-Pugh B9 or in patients with Child-Pugh C cirrhosis—that is few and far between given the fact that you have this competing risk of liver-related mortality and probably marginal, if any, benefit from applying locoregional therapies. Likewise, we typically have cutoffs in terms of bilirubin. We’re very reluctant to give this in a patient, for example, in with a bilirubin greater than 3 mg/dL and other similar cutoffs. But I think when we look at the ideal patient for chemoembolization, it’s somebody with limited tumor burden, good liver function, and good performance status.
Stephen L. Chan, MD: When we assess the patient for whether he or she is suitable for TACE [transarterial chemoembolization], initially we will consider 3 factors. I think the most important factor is hepatic function because most of the patients with HCC will have comorbid cirrhosis and deranged liver function. We know that if the patients have a suboptimal liver function to start with, usually their tolerance and response with TACE will be suboptimal. The better candidates will be those patients with a Child-Pugh class A, or recently some data show that if the patient has ALBI [albumin-bilirubin] grade 1, they will do better than those patients with less optimal liver function.
Apart from the liver function, another parameter that we look at is the tumor burden. We know that BCLC [Barcelona Clinic Liver Cancer] stage B HCC is quite a heterogeneous disease, a patient can have a relatively small tumor ranging to a very big tumor, larger than 7 or 8 cm. The patient can have just 3 or 4 nodules of HCC, or can have a large number of HCC nodules. Therefore we know that when we give TACE to the patient, the disease burden will affect the subsequent prognosis and the response. For those patients with larger disease burden, they are usually not good candidates for TACE.
Different regions have used different criteria to define these types of high burden BCLC stage B. In the West, perhaps more people would use the BCLC B subclassification. In the East, many doctors will use the beyond up-to-7 criteria, which takes into consideration the tumor number and the tumor size. If the tumor is beyond up-to-7 criteria or having a more advanced BCLC subclassification, for example more tumor numbers, larger tumor size, usually they are not doing particularly well with TACE. Therefore, we also consider this factor when we assess the patient for TACE treatment. The final factor is the performance status. We know that for patients with worse performance status, by default they are not BCLC B, versus those patients with a performance status of ECOG 0, for example, they will be a better candidate for TACE. Whereas if they have a worse performance status, they may be considered for other treatment, for example, systemic therapy.
Regarding members of the multidisciplinary team to decide on the initial TACE, usually I would advise a group of 3 specialties of doctors. One is surgeons. The reason is because some patients may have a BCLC stage B, but there are many data showing that for some smaller burden BCLC B disease, they may also be amenable to surgical resection. So a surgeon is important to assess the patient beyond the BCLC criteria. In most centers, if the patient is suitable for surgery, perhaps they will receive surgery as a first-line therapy.
Another group is the interventional radiologists because they are the specialty doctors who are conducting the TACE procedures. They may be commenting on the technical feasibility about the patients’ tumor stages and vascular stages. They are important to the composition of the multidisciplinary team. The last group is the oncologists. The reason is because nowadays we know a group of patients may not be perfect candidates for TACE, so they may be better treated with systemic therapy as upfront treatment. These oncologists will be important for providing opinions to the surgeons and the IR [interventional radiologist] doctors to choose the best treatment for the patient. Even if the patient just has BCLC B, the treatment may be different depending on those 3 parameters that I’ve mentioned.
Masatoshi Kudo, MD, PhD: TACE has been the only standard of care for intermediate stage HCC for nearly 20 years, according to the AASLD [American Association for the Study of Liver Diseases] or EASL [European Association for the Study of the Liver] guidelines. The intermediate stage is defined as a multifocal disease or multifocal nodules, and PS0, and a good rate of function. But in other guidelines, such as the Japan Society of Hepatology guidelines, a single large tumor is also an indicator of a candidate for TACE. Recently, the intermediate stage with high tumor burden, such as up-to-7 outpatient—up-to-7 means maximum tumor diameter plus the number of tumors is more than 7. For example, maximum tumor diameter is 5 cm, and there are 3 nodules, so it’s 5+3=8. That is high tumor burden. Recently, other treatment strategies have been introduced, such as lenvatinib, initially, for such an intermediate-stage patient with high tumor burden. Then the tumor downstaging is obtained. We introduce super-selective TACE, that way we can preserve the liver function as well as get a good response.
Transcript edited for clarity.