Riccardo Lencioni, MD: So, chemoembolization and radioembolization with Y-90 are both widely used therapies for patients with intermediate/advanced HCC. And clearly, they have different indications and different data to support their use in clinical practice. At our institution, we rely primarily on chemoembolization for patients at intermediate stage. Radioembolization is reserved for patients who progress after chemoembolization, for patients who have a limited portal vein invasion—let’s say it’s segmental or branch portal vein invasion—or for patients with very large tumors—let’s say more than 7 cm in diameter. Then we would offer radioembolization over chemoembolization. Chemoembolization is the standard of care for the bulk of the patients at the intermediate stage, which clearly are patients with disease isolated to the liver, no vascularization and no extrahepatic spread.

Patients with extrahepatic disease, let me say that there may be exceptional cases where you may have a truly very limited, sometimes even questionable, extrahepatic disease. These are exceptions that are real in clinical practice. And for some of these patients, we definitely may offer locoregional therapy to the bulk of the tumor, which is in the liver, and under the assumption that that tumor will drive the evolution of the disease and hopefully will have an impact on survival on prognosis.

A different scenario is technically what we usually think with patients with extrahepatic disease, where the disease is truly a systemic disease. I think these patients deserve a systemically active drug with a systemic effect. The question, though, is, to which extent will combining a locoregional therapy really achieve a better control and hopefully a response in the liver tumor burden that will contribute to boost survival? This is a very important area for research, and I think we don’t have much data at this point in time. But definitely, this is something that will deserve further investigation.

Since the advent of sorafenib like 10 years ago, there was excitement in trying to understand the limitations of locoregional therapy, which is typically the fact that despite having achieved sometimes a response, or even a complete response in the target tumors, the disease will come back with new tumors and eventually move from within the liver to outside of the liver. So, there was a lot of excitement on combining locoregional therapies with drugs, in particular with sorafenib.

Now the bottom line after several years of research is that the synergy is probably less than we thought. There may be some prolongation in time to progression, but the impact on the survival is not very clinically meaningful. Of course, at this point in time, with more drugs becoming available and different concepts—TKIs, immune checkpoint inhibitors—I think it’s easy to anticipate a second wave of clinical trials that will investigate the synergies. Personally, I believe that’s the way to go, and I’m very confident that eventually we will find a combination that will be able to offer sustained minimal invasive control of the visible tumor relations with a systemically active drug that would prevent or delay recurrences, thereby boosting overall survival.

Transcript Edited for Clarity