Amid Explosion of Novel Agents, Surgery Remains Critical in Melanoma

Kiran K. Turaga, MD

Surgery in melanoma has become standardized and efficient, explains Kiran K. Turaga, MD, but ongoing trials are exploring novel methods for more melanoma subsets.

In the phase III randomized FOCUS study, researchers are evaluating the efficacy, safety, and pharmacokinetics of a percutaneous hepatic perfusion with melphalan/HDS treatment versus best alternative care in patients with hepatic-dominant ocular melanoma (NCT02678572). Investigators will be using overall survival as the primary endpoint.

“There are a lot of options, lots of excitement, and lots of advances that are happening in the surgical space—as well as the interventional radiology plus surgery space,” said Turaga, associate professor of surgery, vice chief, section of general surgery and surgical oncology, director of the Surgical GI Cancer Program and the Regional Therapeutics Program at The University of Chicago Medicine. “This is paralleling the progress that’s happening in the immunotherapy space, as well as the lymphocytes and everything else. It is an exciting time to be a melanoma surgeon.”

In an interview during the 2017 OncLive^® State of the Science Summit on Melanoma and Immuno-Oncology, Turaga spoke on how surgical approaches have advanced in the treatment of patients with melanoma.

OncLive: You discussed surgery in your lecture. Can you provide a summary?

Turaga: It is important to remember that surgery remains to be the mainstay treatment of melanoma. If you think about it, surgery has roles in 3 big groups: management of the primary lesion, management of the nodal disease, and management of metastases.

As far as the primary disease goes, I don’t think there has been much of an advance in what we have to do. It’s very well established and well studied. Taking the melanoma out with good margins is sort of the standard way of approaching this and is very curative for the majority of thin melanomas.

The assessment of the nodal base has gotten a radical transformation over the last decade, and more so over the last few years. We do know that the advent of the sentinel lymph node biopsy was very important in staging the nodal basin and how it is associated with the melanoma. We found out that there is more beyond the prognostic significance of the sentinel lymph node biopsy; that has been challenged with the Sunbelt Melanoma trial and the DeCOG-SLT trial. Both found that, for micrometastases, you don’t actually have to do a complete node dissection.

The survival rates are similar for both groups of patients. It’s a very interesting concept that we are kind of evolving into the space. We always started with node dissections being the standard of care and now it’s no longer necessary for people with micrometastatic disease.

What has also evolved in the surgical space is the ability to do these node dissections in a less morbid way, whether it is minimally invasive surgery, robotic surgery, or laparoscopic surgery. We can actually do minimally invasive groin lymphadenectomies.

While on the one front we are finding that perhaps we don’t have to do node dissection for everyone, we are also finding that you can do these in a less morbid way. We are going to come to a head, hopefully, in the next few years, where we'll actually be able to clearly define the balance of who needs surgery and who doesn’t.

What is exciting is for in-transit metastases. While there are local therapies, such as talimogene laherparepvec (T-VEC; Imlygic), local injections, or immunotherapy, the in-transit space also has isolated limb infusions and perfusions. Here, we can actually put catheters into the leg or arm and perfuse it with chemotherapy. We are finding that this makes these tumors highly immunogenic. Therefore, the potential combination of immunotherapy with isolated limb infusions for local regional control of metastatic disease is a very exciting area that is also ready to evolve.

Finally, with regard to metastases, metastasectomy has always been a part of management of metastatic melanoma. Even now, we know that when patients have bulky disease, they don’t respond as well to immune-based therapies. Therefore, surgery plays a role [in patients with metastases]. What is exciting is the fact that we can actually do perfusions to save the liver.

Do you find that, with the immunotherapy advancements, more patients are opting for these treatments over surgery?

For primary melanomas, or for melanoma that is nonmetastatic, surgery is still the standard of care. In that area, we don’t see any kind of change. In general, if there are clinical trials for metastatic melanoma, then that is the best way for patients to go. Whether it’s immunotherapy-based, anti-BRAF therapy, or surgical perfusional, clinical trials are number one. That is my personal preference, and I would encourage others that if they have a clinical trial available, that is the best way that these patents should go forward.

In the in-transit disease, there are certainly issues. While there are therapies such as isolated limb infusions and perfusions, which are fairly low morbid, they can be alternated for immunotherapies—which hasn’t been studied as well for in-transit disease.

I would caution community oncologists or others who are treating patients with these melanomas to make sure that the patients have had a full flavor of their options available to them and that the treatment option that is most suitable for them be applied. In some cases, it is surgery and limb infusions and, in others, it is immunotherapy or anti-BRAF therapy. In terms of thinking about patient preference, a lot of patient decision making is when you talk about the efficacy of your treatment versus the morbidity and longevity of it. Those can really play an important way in the way you phrase it.

Surgery is a one-time event. While it may sound less morbid to take a pill or get an injection every 3 weeks for the next 3 years, there is a big dramatic difference in terms of the longevity of these treatments. It is all about how the patients are approached and it’s very multidisciplinary. I don’t think any one treatment is far superior to the others.

What are the most common adverse events associated with these surgical procedures?

It varies. In the big groups, with regards to just excisions, it’s mostly cosmetic or small issues with problems. It is fairly straightforward; we are in a much better surgical way now with flaps, free flaps, and things like that. We can do lots of things for local care.

From a nodal standpoint, the biggest thing we worry about is lymphedema, which is one of the concerns we have when we do node dissection. With minimally invasive surgery, better definition, and better visualization, we may get better at that. There are now surgical options for lymphedema, so you can actually do lymph node transfers.

For metastatic disease, it depends on what is being done. It could be very minor since we can do things robotically, laparoscopically, or minimally invasive. Or, it could be something fairly major if we do a big perfusion.

What ongoing trials are you anticipating to see the results of?

There is the MSLT-II trial, which will likely have results in 2022, which is very exciting. It’s a large, randomized trial looking at patients who have positive sentinel lymph nodes and undergo completion or dissection versus observation alone. That is an interesting trial that’s out there.

Secondly, there is a phase II trial looking at immunotherapy with isolated limb infusions. We are part of a trial at The University of Chicago Medicine, which Dr Jason Luke is the principal investigator of, for hepatic perfusion for metastatic melanoma.

What are the main points that you hope community oncologists took away from your lecture?

For people to realize that there are options that are surgical or regional for both patients with locally advanced disease as well as for metastatic disease. There are significant surgical advances that have happened in the management of nodal disease since some of these physicians were fellows or in training.

There are certainly lots of advances that have happened in this space and, at any point, it’s easy to reach out to someone who may be interested in melanoma surgery, specifically at The University of Chicago Medicine.