Expert Highlights Advances With Locoregional Therapies in HCC

Emil Cohen, MD

Technological advances made in interventional radiology have allowed for more accurate treatment delivery, leading to stronger responses in patients with hepatocellular carcinoma (HCC), said Emil Cohen, MD, and combination approaches may be key to achieving better outcomes.

Transarterial chemoembolization is the current standard of care for patients with intermediate-stage HCC, however, it is not without limitations. For patients whose tumors are small enough in size and are in a favorable location, percutaneous ablation is another available approach.

“The best option would be to get them to transplant,” said Cohen, an assistant professor at Medstar Georgetown University Hospital. “If it's not safe to do an ablation technology, you want to at least get them to palliative treatment, which is chemoembolization. Sometimes we combine the two as well.”

For those who cannot undergo transplant, investigators are exploring several approaches that they hope will downstage the tumor so that patients can become eligible. Among those approaches are radioembolization, external beam radiation, aggressive resection, or a combination of these modalities.

“There have been studies that have shown, for instance, that if you do radioembolization compared with conventional chemoembolization, you have a much better chance of downstaging a patient to get them to transplant at some point,” added Cohen. “Someone who wasn't a transplant candidate becomes a transplant candidate. External beam radiation has shown a lot of promise. It still needs to be further worked out because there are not really randomized trials [with it], but I'm really hopeful.”

In an interview with OncLive^®, Cohen discussed the locoregional therapies available for the treatment of patients with HCC and offered insight into optimal strategies.

OncLive: Could you briefly describe the most common types of locoregional therapies used in HCC?

Cohen: The most commonly accepted [therapeutic approach] for HCC is some form of chemoembolization, whether that be conventional or with drug-eluting beads. That's the standard of care. [Another type is] rabioembolization. Some [providers] have even been using bland embolization; that is the least popular type. If you're going with a standard intravascular treatment for patients with HCC with chemoembolization, that's the transarterial route. You can also try to ablate these tumors percutaneously. That also falls under our purview with heat or cooling, which is known as traditional radiofrequency. Most recently, in the past 5 years or so, microwave ablation has become more popular, since it is not as susceptible to some of the limitations [often experienced with] radiofrequency ablation.

What are the pros and cons of each of these approaches?

The transarterial routes are limited by the fact that they're mostly palliative. They get a response rate that's [in the range] of 50% to 75%, which means that you [are able to] keep the tumor the same size or hopefully shrink it. Ablation technology, provided that the tumor is in a good location and small enough in size, can have cure rates ranging from 90% to 95%. Therefore, if we can ablate [a tumor], we would rather do that, because we're going for a cure as opposed to palliation. Having said that, the caveat is that most patients who are transplant candidates, which would be the ultimate treatment for a patient who has cirrhosis, are being bridged. You want to minimize the risks while you are maximizing the benefits. The standard of care for those patients is chemoembolization. I always keep in mind that curing is not necessarily the only option for a patient.

Which patients are candidates for ablation?

Patients are eligible for ablation if they have a tumor that's reasonably sized and in a good location. It's just like real estate: location, location, location. When a tumor is very large, it makes it harder for our heat to completely destroy it, so [with tumors] up to 3 cm, we have a 90% cure rate. However, after 3 cm, the cure rates drop significantly. I treat tumors up to even 5 cm or more, but I go in there telling the patient, "Look, this is much less likely to be successful at getting rid of the entirety of the tumor."

We have other options available now, such as combining chemoembolization with ablation, which is what we are frequently do, or even doing radioembolization or external beam radiation. We have to weigh [these approaches] evenly. Where 5 years ago we were being much more aggressive with [this treatment], we're [now] trying to [discuss these cases] with our multidisciplinary groups to try to come up with the best solution for each individual patient.

What long-term outcomes data exist for patients who undergo locoregional therapies?

That's a good question. The original data for conventional chemoembolization came back in the early 2000s with 2 studies. They showed that doing chemoembolization prolonged life and time to progression, so that, in itself, is the reason that [this approach] has become standard of care. We don't have randomized trials showing that this actually benefits someone who is awaiting transplant, but [those trials are] never going to exist.

Newer studies that are superseding regional therapy as standard of care haven't been done in transplant-eligible patients, because [this is a group that is] still waiting for transplant. Physicians and hospitals are very careful to treat these patients and keep them in that transplant pool. Patients don't realize that even if we cure someone who has cirrhosis, they still have a 2% to 7% chance per year of [developing] a new cancer somewhere else [in their liver]. Therefore, I always tell my patients, "Alright, look. We're hopefully going to get rid of this thing. But even if we do, and you come back to my office and we've cured your cancer, that doesn't mean you don’t have to go to your transplant evaluations. You have a 2% to 7% chance of getting a new tumor in your liver, and that adds up over the years. This means that if you're alive 10 years from now, you're talking about a 20% to 70% chance of having a new tumor [emerge] in your liver.” Therefore, we want to be very careful with patients who are transplant candidates.

If we go past that, and we have patients who are not transplant candidates, there has been a lot of work dedicated to exploring a multitude of different [approaches].

What steps should be taken after a patient fails on locoregional therapy?

The key thing to remember is that individual modalities, whether it be chemoembolization, drug-eluting beads, or radioembolization, work in different ways. We have patients who respond to one treatment but don’t respond to another. Once patients have failed the [treatment], oncologists now have so many new systemic treatments [to offer], such as immunotherapies, which are showing great promise. It would be great to put these patients on those studies to try to help them achieve better results.

Are there any ongoing trials that you’re excited about in this area?

We're excited about a trial [being conducted at my institution], where we are injecting a virus into a tumor to induce apoptosis in the hopes that giving immune modulators, along with exposure of the antigens that apoptosis brings about, will induce a much better response systemically. Before this trial, there have been some earlier studies that have shown great promise. Therefore, we're excited about implementing the study to see if we can help patients with it.