Locoregional Therapies Remain a Key Element of Care in HCC

Riad Salem, MD

A number of treatment options exist for patients with localized hepatocellular carcinoma (HCC), including surgical resection, transplantation, ablation, stereotactic body radiotherapy (SBRT), and embolization, said Riad Salem, MD, who added that a multidisciplinary team is needed to determine the optimal use of these approaches among newer novel systemic treatments.

"When I think about the options that exist now, there will likely be some centers that apply systemic therapy in patients who may be candidates for local therapy," said Salem. "It is inevitable given the strength of the evidence, but I wouldn't downplay the importance of local therapies."

In an interview with OncLive, Salem, a professor of radiology, medicine, and surgery, vice chair of Image Guided Therapy, and chief of Vascular Interventional Radiology in the Department of Radiology at Northwestern University Feinberg School of Medicine, discussed the role of localized therapy in HCC, the need to personalize treatment for patients, and the importance of implementing a multidisciplinary approach in this setting.

OncLive: Could you discuss the role of local therapy in the treatment of patients with HCC?

Salem: As an interventional radiologist, I try to [promote] the idea that we can combine local, regional, and systemic therapy.

Many patients may benefit from combination approaches. In general, we study [the impact] of applying a combination of local regional therapy, even for patients with advanced disease, and therapy that may be perceived as the standard of care, such as systemic therapy.

For example, let's say a patient has portal vein thrombosis with vascular invasion but no metastases. That individual has localized disease. However, we believe we can optimize treatment by applying local therapy and then implementing systemic therapy 4 to 12 weeks later.

There's no doubt that there are challenges with generating high level 1 evidence with [local therapy], but the reality is that many patients do not fit strict inclusion criteria for clinical trials. It is difficult to demonstrate this paradigm with 1000 patients in a randomized clinical trial, but it makes a lot of sense. We have to figure out ways to use data, triangulate information from multiple studies to determine the best approach [with local therapies]. For some patients, [local therapy] can postpone toxic systemic therapy. By combining [therapy in this manner], we can optimize [the patient’s care] and expose them to all of the agents they would be good candidates for.

What options are available for patients who require localized therapy?

Local therapies, such as surgical resection, transplantation, ablation, SBRT, and embolization are indicated when a patient has localized HCC. There are different [ways] we can apply [these modalities].

We are trying to figure out which patients benefit most from which [approaches]. It is a work in progress, and the decisions are based on experience. [Those of us who work] at centers with a lot of experience in a certain [specialty], tend to favor that treatment over another. Therefore, it is based on opinion in many places. It is also based on available evidence. In early-stage disease, a lot of the data we have with local therapies is from phase 2 trials. We try to work together in a multidisciplinary manner to develop a plan to provide the best treatment option for the patient.

How could the influx of systemic therapies impact the role of localized therapy?

It is a very exciting time. The last 3 to 5 years have provided us with level 1 evidence regarding therapies that improved overall survival compared with the standard of care. The newest data from the IMbrave150 trial are just shy of spectacular.

However, most of the patients [included in IMbrave150] had extrahepatic metastases. There is clearly a patient population that should benefit from the combination, but there are patients who have more localized disease where adding a local therapy makes a lot of sense. Eventually, when some of these patients progress or become intolerant to the local therapy, it makes sense to stage-migrate to a systemic therapy.

There are a lot of tools, so we have to figure out how to formulaically apply each tool to each scenario.

Localized therapies are often one-time treatments. The quality of life is typically excellent. We have to make sure we identify which patients should be given localized therapies. We have a lot of treatments available, but we need to get better at figuring out which patient should be treated with which regimen in which scenario.

Could you speak to the importance of incorporating a multidisciplinary approach in the treatment of patients with HCC?

Patients with HCC are often managed by interventional radiologists, medical oncologists, and hepatologists. They are shuffled back and forth from these specialties because, in reality, that is how we manage patients. [We treat patients] with what we have expertise in to try to figure out what the best treatment is at a specific time for a particular patient. Sometimes the patient is downstaged [and given a curative approach] with resection or transplant. It is very important to keep all of these [specialties] involved.

It is not uncommon that we represent patients we manage in a multidisciplinary tumor board to discuss whether there is something else [we can do]. Perhaps we can ablate the patient or reset something; perhaps the surgeon has a new idea we can try. We discuss patients frequently [in tumor boards], which in my opinion, is the best way to manage them. Ultimately, that is the spirit of a multidisciplinary tumor management paradigm.

What are some remaining questions in this space? How do you see the HCC paradigm evolving over the next 5 to 10 years?

The struggle, of course, is that recurrences occur. We need to figure out ways to start thinking about curing patients in the advanced setting. We should be looking to see what we can do to help our patients because it is possible to achieve cure, even if it is in a small percentage of patients who [present with] advanced HCC.

Looking ahead 5 to 10 years, we want to figure out ways to delay progression for years because then patients are effectively cured and have controlled disease. We want to figure out ways to stage-migrate patients with more advanced disease to the left side of the Barcelona Clinic Liver Cancer [staging system] to curative approaches. Liver transplant, while a good option, is limited by organ availability. Are there ways to make patients more resectable? What biomarkers can be used to help guide treatment options for patients? These are some of the [questions] we are working to answer.