Monotherapy vs Combination Treatment Options for Solitary Liver Cancers

Treatment of hepatocellular carcinoma (HCC) continues to rapidly evolve, and interventionalists are confronted with an array of treatment options. Charles Ray, MD, PhD, an interventional radiologist at the University of Illinois College of Medicine in Chicago, spoke at the SIR meeting in Austin, Texas about monotherapies, combination therapies, and other factors affecting treatment decisions for HCC.

Are monotherapies or combined treatment strategies preferred for hepatocellular carcinoma?

Monotherapy, meaning an interventional therapy without systemic therapy or systemic therapy without an interventional therapy, is becoming less common. Instead, we often perform a combination of therapies in collaboration with either medical oncologists or radiation oncologists. There are also some combinations of therapies that we can perform with two different modalities that fall within the practice area of interventionalists, such as chemoembolization plus ablation therapy rather than ablation therapy alone.

The data are numerous, and essentially they have all shown that combination therapy is more advantageous than monotherapy consisting of chemoembolization or ablation alone. The decision regarding whether ablation therapy comes first followed by chemoembolization, or whether chemoembolization is first followed by ablation, is operator dependent, and there are no data showing that one treatment order is definitively superior. Most operators will perform both treatments in the same setting or within 24-48 hours, although there are no firm data that even show that the 24-48 hour interval is more beneficial than a different interval.

Other combination therapies include drug-eluting bead therapy and microwave ablation versus radiofrequency ablation. There was a featured abstract at SIR last year that looked at that particular question: Are drug-eluting beads plus radiofrequency any better than drug-eluting beads plus microwave? The results showed that nothing reached statistical significance, but there was a trend, a P-value of 0.09, that showed that in the combined setting microwave had fewer recurrences than radiofrequency.

What are your thoughts on radiation segmentectomy versus combination therapy for solitary HCC?

There is one retrospective review that specifically addresses that question. The endpoints in that study showed that there was no difference between those two types of treatment. One can certainly postulate that there will be certain patient populations in whom the lesion might not be ablatable or in whom doing radiation therapy or radioembolization might be too dangerous. In such scenarios, the other modality will have a clear advantage. The bottom line, though, is that every interventional radiologist should know how to do each of these procedures so that they can tailor patient care as needed, because scientifically there often is no reason to do one procedure over the other.

What role does operator preference play? Is it better to focus on becoming highly skilled at one procedure?

That’s a good question, but I still think it’s important to cultivate skills in both areas. There will be times when one of the options is not possible. It is best to know how to do both procedures, even if you don’t perform both of them frequently. If the patient needs a procedure that you do not perform frequently, then you have to make a judgment call – is it better for you to send the patient to someone who performs the procedure more frequently, or can you handle this patient on your own?

What are the most important points to remember regarding combination therapy?

When comparing combination therapy with ablation therapy, it’s important for interventionalists to know that the data overwhelmingly favor combination therapy. However, when evaluating radiation segmentectomy vs ablative therapy, there are not enough data right now to definitively favor one over the other. Until we have more data, the decision is a matter of operator preference.

How do cost and technical factors affect treatment decisions?

One study examined the treatment for recurrent HCC. Patients who had recurrence following hepatectomy underwent either radiofrequency ablation or chemoembolization, not combination therapy. The study showed that if patients in that population had a second recurrence, they would have better outcomes with the alternate therapy compared with the first line of therapy that they had after the first recurrence. For example, if the patient underwent chemoembolization after the first recurrence, they would have better outcomes with ablation after the second recurrence, and vice versa.

Can you comment on systemic treatment with sorafenib and how that plays into treatment decisions?

Right now, sorafenib is the best and most well-studied medication in terms of systemic therapy for HCC, but there are many drugs in the pipeline that will probably be equally efficacious, or more efficacious, but with a better side effect profile. If a new drug is as effective as sorafenib but with fewer adverse effects, then that new drug will probably become first-line therapy.

Any other takeaways from your presentation?

For a long time, we have used the Barcelona Classification for Liver Cancer (BCLC) to guide treatment. However, we are now extending our treatments and blurring the lines of traditional classifications, and so are the medical oncologists, surgeons, and radiation oncologists.

In the last year, there were seven thousand articles published on HCC. The field continues to explode, and treatment paradigms are changing rapidly.