Expert Shares Optimism on Surgical Advances in Melanoma

Russell Berman, MD

Practitioners today are having much different conversations than they did in the past regarding the treatment options for patients with melanoma who have non-nodal metastases or regionally advanced disease, according to Russell Berman, MD. Moreover, thanks to refined techniques, select patients who were not deemed eligible for surgery are now able to undergo it.

“It is an incredibly exciting time to be involved in melanoma, which sounds a little odd, but it’s actually true,” explains Berman. “At the large oncology conferences, melanoma was once confined to a small, offshoot room in the corner and wasn’t at the plenary presentations. [Now], we have certainly dominated the plenary presentations and [have had very] exciting developments over the past few years.”

OncLive: What did you discuss in your lecture on melanoma?

In an interview during the 2017 OncLive^® State of the Science Summit^TM on Melanoma and Immuno-Oncology, Berman, division chief of Surgical Oncology at New York University Langone Medical Center in New York, shared his enthusiasm over ongoing surgical advances in the treatment of melanoma.Berman: I spoke about non-nodal regional metastases, which, in melanoma, we refer to as in-transit metastases. I also spoke a little bit about systemic metastasis. Now, what is fascinating is that, with new systemic therapies that are effective for melanoma, such as the checkpoint inhibitors in targeted therapy, people think, “Well, is surgery no longer applicable? Do we ever need it again?” In fact, it may actually be defining a role for surgery that we didn't previously appreciate.

A lot of time when we have these advanced diseases—be it multiple in-transits, unresectable in-transit disease, or systemic metastases—in the past, we would only operate on very select people with it. It was maybe 1 or 2 metastatic lesions that were relatively easy for us to get to without causing a lot of potential harm to the patient.

What advancements have you seen in surgical therapy for melanoma?

Now, patients who we never would have considered operating on because of the quantity of metastases, [might] respond to the systemic therapy, and then only have a few persistent lesions—1 or 2 or 3. Then, they all of a sudden become surgical candidates, and they had not been previously before. Rather than thinking of it as, “Well, gee, no longer do we need surgery for melanoma,” it is quite the opposite. We really choose these selected people who would benefit most. It is actually an exciting time. We have refined a lot of surgical techniques. We were taking out huge margins 40 years ago that were incredibly debilitating and doing large lymph node dissections with potentially no significant benefit to those patients. We did that routinely, and we thought we were truly doing the right thing. That has evolved over time to the point where our margins have decreased in size based on data and worldwide randomized trials. There is actually science behind it.

The results of the long-awaited MSLT-II trial came out, which continues to have the lymph node dissection story evolve, and that clearly is a game changer in terms of whether or not to complete a lymph dissection—although there are still some variables that we haven't truly examined.

Then, of course, there is advanced disease. Previously, if I could not help patients with regionally advanced disease in any way, shape, or form, there were not many other options. Sure, we had our medical oncology colleagues come in, but they didn’t have really effective therapy.

That’s great to hear. You mentioned the MSLT-II trial. What other ongoing trials in this space right now are you excited about?

It has totally changed now with the checkpoint inhibitors and targeted therapy. When I have patients with advanced regional disease or systemic metastasis, the entire conversation has changed, the entire mood has changed, and the outcomes have changed. It has truly never been a more exciting time to be a melanoma surgeon or a melanoma practitioner. On a metastatic front, there are things such as brain metastases, which, previously, weren't included in clinical trials. Now, all of a sudden, we have multiple abstracts from the 2017 ASCO Annual Meeting, which is truly encouraging. That’s a space that nobody would ever go to previously. It really has evolved tremendously.

From the surgical side, the MSLT-II trial was long awaited. There had been some small trials—the DeCOG trial out of Europe, for example—but the MSLT-II multinational study was very well designed and executed. We’ve been waiting a long time for the results. The editorial that accompanied that result in the New England Journal of Medicine clearly stated that completion lymph node dissection is not the standard of care.

There are still a few areas that we need to look at: patients with large-volume disease in the sentinel node, and patients who have multiple sentinel nodes removed to have positive disease multiple sentinel nodes. Plus, we need to not forget that the observation aspect of the MSLT-II trial was ultrasonography surveillance of the nodal basin at risk, and there may be institutions that are not ramped up to doing that ultrasound observation.

What other unanswered questions might still exist for surgery in melanoma?

What do we do in that setting? There are clinical trials ongoing with systemic therapy or adjuvant therapy, where completion lymph node dissection is still considered the entry criteria to those adjuvant trials. We will have to make a decision on what to do with that. The story is not entirely written yet.What I’m speaking about—non-nodal regional disease—I find to be more fascinating, especially the in-transit disease. These cases are the ones that have basically palpable or visible lesions between where the primary tumor site was and the first nodal basin that drains that primary tumor.

What do you want community oncologists to take away from your lecture in this area?

It’s a pattern of metastasis relatively unique to melanoma, and it is palpable. When it’s palpable, that means we have access to the tissue easily. It is an incredible opportunity for us to run translational trials where we can get the biopsy prior to initiating checkpoint inhibitors or targeted therapy, then get more tissue during the time that we’re having treatment, and then to see what the end result is. If there isn't a response, we could always surgically salvage as I had mentioned before. What better paradigm [is there] for translational research?It is a very different era for melanoma. In years past, when we had patients with extensive metastases—an entire leg full of in-transit disease—we said, “Well, gee, is this it? Should we be just providing comfort care?” Of course, we can never forget that aspect of things; however, what I would have considered as “not treatable for potential cure” in the past, I don’t [consider it that way] anymore. [Clinicians are] cautiously optimistic; that’s been true for even the most difficult and challenging patients I have seen. It is a different playing field compared with years past.