The Latest Trends in Melanoma Care

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a medical oncologists here at Cleveland Clinic overseeing our Taussig Phase I and Sarcoma programs. Today I'm happy to be joined by Dr. Anthony Visioni, a surgical oncologist at Cleveland Clinic Akron General. He's here today to talk to us about upcoming clinical trials and trends in the care of patients with melanoma. So welcome Anthony.

Anthony Visioni, MD: Thank you. Thank you so much for having me. I'm excited to talk a little bit about a topic that I feel a bit passionate about.

Dale Shepard, MD, PhD: Excellent. So maybe to start out, you can give us a little background on your role here at Cleveland Clinic.

Anthony Visioni, MD: So as you mentioned I'm a surgical oncologist, so generally speaking, my practice is fairly broad. I treat a lot of complex gastrointestinal and other types of malignancies across the spectrum. And obviously one of those focuses on cutaneous malignancies and melanoma. So I got an interest in this actually going back as far as my residency, where I did research in immunotherapy of melanoma back when I was a junior resident and I carried that interest forward. So that's a little bit about where I started from to get to where I am now.

Dale Shepard, MD, PhD: So from a surgical standpoint, what do you see in terms of the current management of melanoma? What do you find exciting? Let's just jump into to what do you find most exciting about surgical management of melanoma right now? We hear a lot about immunotherapies and things, but we'll talk about how maybe that ties in, but from a surgical side, what do you see?

Anthony Visioni, MD: Let's say that there's kind of been a pretty big shift in melanoma surgical care recently. So to take you back a little bit, the standard of care for melanoma for early stage non metastatic melanomas has been a wide local excision and then staging with a sentinel lymph node biopsy has been really established since the 1990s or so. And that's been the standard of care for a long time. The implications of a positive sentinel lymph node have usually meant that we would go on to perform a completion lymph node dissection in the affected basin. And so for decades, we would be offering patients completion lymph node dissections pretty routinely.

A lot of times, patients didn't want to go through with this, quite frankly. So even at the timeframe where this was the standard of care, it was probably only done about 60% of the time. Patients would really defer it. And the reasoning is usually because about 80% of the time we did these operations, there was no residual melanoma in the lymph node basin. So a lot of times we weren't seeing that benefit from the disease being present. And it comes with some morbidity, particularly lymphedema in affected extremities. And that can be quite debilitating to the patients that have it.

So this prompted some studies that were done, and actually just recently published, most notably a study called the MSLT-2 Trial, which was published in 2017-18, and really, quite frankly, it was a big paradigm shift for our care. And, more or less, the punchline of the trial says that if we take a patient with a positive sentinel lymph node and observe them, or go ahead and do a completion lymph node dissection, there's really no difference in their survival. And I think that this goes to show a little bit of the fundamental lack of understanding we truly have about the biologies of cancers. When we're gaining traction, and learning so much more, but just because you have disease in a lymph node, doesn't mean it's going to affect your overall survival. And that's really changed how we approach melanoma care today from a surgery perspective.

Dale Shepard, MD, PhD: So back to that trial, were there any subsets of patients that we still would say, certain characteristics, your primary tumor, we're still going to move forward with lymph node dissection then, is that easier or more difficult to sell now to a patient?

Anthony Visioni, MD: Yeah, it's a great question because this is a trial that I feel like the surgical oncology community and the melanoma community really embraced and shifted our care, but we do find nuance to it. And we do find some discussion points with patients. Because I think it's important not to just do a wholesale blanket pattern of care to say you don't need it anymore. So I still do have a fairly nuanced discussion with my patients. So one of the particular subsets that we are concerned about is head and neck melanomas. Those in general have, in the past, been shown to be a little bit worse off actors. And in particular lymph node recurrence in the head and neck area can be a little bit of a different biologic beast, so to speak. We don't see lymphedema in the head and neck, quite frankly, that's not something that occurs as much and the morbidity of those dissections can be different. We worry about nerve injuries, maybe a little bit more, but in an experienced hand that's pretty minimal.

So what we really worry about in the head and neck region is actually loss of control. If we have a local recurrence in the neck, we worry about the major vessels or nerves in that area and how they be effected. And that would be different than the groin or the axilla where we do worry about a loss of local control, but it's much more salvageable. So we do have a little bit more of a nuanced discussion with patients, particularly in the head and neck field. It still was included in the trial. So the trial did not stratify by any particular region. So I think it's fair to have a patient select to not have that completion lymph node dissection, and just go with observation. But we do observe them very closely. I do nodal ultrasound on them every four months and we really keep a very close eye to make sure we don't have any of that loss of local control.

Dale Shepard, MD, PhD: We had a previous episode of this Cancer Advances Podcasts. We talked to Dr. Schwartz about lymphedema management. And do you find that you work with the plastic surgeons and the guys doing lymphedema work on those patients that you do still do lymph node dissections?

Anthony Visioni, MD: I absolutely do. So I'm very proactive about really getting plastic surgery involved very early in their care and really trying to manage lymphedema with that ounce of prevention. So the more we can have that be a controlled problem or a problem that we avoid completely, the better off that patient's going to be in the back end. Because it can be quite a debilitating disease.

Dale Shepard, MD, PhD: Now you mentioned head and neck being sort of its own characteristics. Patients of course get treated in a variety of different settings here on our main campus, Akron General, where you're in the community.

Are there particular patients that you think really should see you who kind of have more of an interest in those kinds of nuances? Is there a particular subset of patients that you really want to make sure everyone sends your way?

Anthony Visioni, MD: Well, just from my training, my background, and my practice, I do treat all melanoma. So I will treat head and neck and extremity, truncal melanomas. I know dermatologists are fairly facile and fairly comfortable treating some very early stage melanomas or in situ disease, but I will say there's really no patient who I don't think I can help or that we can benefit from. So even those early stage or in situ patients, I'm more than happy to see. I'm more than happy to work with, obviously even metastatic melanoma patients who may actually have some surgical options, which we can address a little bit too.

So I try and be as full service from a melanoma department as I can. Then obviously there's some really particularly nuanced ones that I really like to involve my colleagues with plastic surgery or head and neck surgery where ear canal melanomas, eyelid, that is a very special and nuanced practice that I try and involve as many colleagues as I can get the best results.

Dale Shepard, MD, PhD: Now, in terms of that multidisciplinary collaboration, how have you adapted to working at Akron General, which for those listening, it's a large hospital, but what about an hour from our main campus? How do you coordinate in a way with main campus and what does that collaboration look like?

Anthony Visioni, MD: Yes, I think from the patient perspective, their willingness to travel an hour up to main campus is sometimes limited. So most of the patients are coming from even an hour south of me. So, what we try and do, I think is I try and collaborate with main and campus through our tumor boards. So for patients who have some nuanced aspects of their disease, or we have some ambiguous findings that may be present, sometimes melanoma pathology isn't always as straightforward as it seems. That's where our main campus cutaneous malignancy team is absolutely second to none. They're phenomenal. And so I collaborate with them through that, and then a little bit offline too, just our contact with each other, to run things by each other as well. And then we do have our medical oncologists down here who have some expertise in melanoma as well. And we do run our more straightforward melanoma through our multidisciplinary tumor board here at Akron General.

Dale Shepard, MD, PhD: What kind of research excites you right now in the field of melanoma? And you mentioned the trial that hanged the way we think about sentinel nodes and lymph node dissections. What else is exciting from a field moving forward?

Anthony Visioni, MD: Yeah, so dovetailing off our discussion about multidisciplinary care, this I think, is a really amazing time in melanoma care where the individual trials that are happening potentially in surgery and within medical oncology really dovetail off of each other and build new trials. So if you go onto the NCI and look at melanoma trials, there's over 300 trials now happening in melanoma. And a lot of them, I think last time I counted is over 50 trials, actually have to do with neoadjuvant treatment of melanoma. So patients who may have forgone a lymph node dissection and present with then a recurrence or patients who present with palpable lymph node disease and are going to get a therapeutic dissection, we're actually considering those patients for neoadjuvant therapies, either immune or targeted therapies to see if we can increase those response, limit our surgical impact and our morbidity from surgery as well. And those are kind of ongoing trials around the country. And those are really exciting to me.

There's also trials looking at, as we see the great responses of adjutant treatments for stage III melanomas. We wonder how we can improve that response even more. So melanoma is a very straightforward disease, except when it's not. And there are several certain caveats to melanoma that are actually pretty interesting. And one of them is that high risk stage II melanoma patients actually have worse outcomes than low risk stage III melanoma patients. It's a very weird nuance of the disease. And so we're actually now studying, and the Cleveland Clinic actually is part of this trial. It's a multinational institutional trial where we're looking at high-risk stage II melanoma and treating those patients with adjuvant immunotherapy to see if they have a better overall survival. And those are really exciting to me because I think we can really, truly do a lot of good impact on patients.

Dale Shepard, MD, PhD: Is there anything new going on from a technique standpoint, from the way the surgeries actually are being done?

Anthony Visioni, MD: Yeah so there's a couple of things in particular that I do and that I find have been well-established, but not as well distributed. And I think that comes from a comfort level. So one of the things that I think has been tried in the past and has been continually on is something called endoscopic lymph node dissection. So particularly in the inguinal lymph node region, one of the issues with doing a lymph node dissection in the inguinal region is a really significant rate of wound and morbidity. So we do see about a 50% wound morbidity rate in the groin.

So an endoscopic dissection really will limit that wound morbidity. Doesn't necessarily reduce our risk of lymphedema, but if we can reduce our risk of wound morbidity, then those patients can potentially get onto their adjuvant treatments even faster. So doing things endoscopically, in an experienced hand, I think has the same outcome as doing it open. And that is, I think, an important caveat. You really have to know what you're doing with an endoscopic surgery on these patients and have pretty nuanced touch with endoscopic techniques to do a really good lymph node dissection. So that's something, I think, that is becoming more comfortable in advanced. It's something that we do down here at Akron General.

Then there's some stuff that's as sacred as the margins of melanomas. Even simple things like that, we're still questioning. So there's another trial going on actually in Australia, which has the highest rates of melanoma in the world. So they can have enough patients to figure this out. It's called the MelMarT trial where we're looking at the margins we take. So gosh, you go back 40 years ago, we used to take a two inch margin around melanoma. That's five centimeters. It's an incredibly morbid procedure to do to people. And that's now established where we really never need to take more than a two centimeter margin, but we even questioned whether we need to do that. So I'd say most of the patients that we operate on, we can typically close their wounds primarily, but if we can shrink that margin down, even more than that would even allow us to do less free flaps or skin flaps and even do more primary closures, which in theory would have better outcomes. So even something as sacred as our margin, we're still questioning and seeing if we can improve.

Dale Shepard, MD, PhD: I'm guessing if there's a thought that neoadjuvant shrinking things down and controlling things looks successful, then maybe that would shrink margins even more.

Anthony Visioni, MD: Yeah. And there's another trial that's going on that is looking at high-risk thick melanomas and performing neoadjuvant treatment on those both to control potentially high-risk metastatic disease. And then yes, to figure out, do we need to do as wide of margins on these patients? Can we contain that even more? So I think as I said earlier, the rolling dovetail about how surgery and medical oncology aspects of things inform each other is really fascinating, and I think very exciting because I would tell patients maybe five years ago when I saw them that the standard of care is kind of a standard of care, but now I tell them in five years, I don't know what it's going to be truly because it is moving that fast.

Dale Shepard, MD, PhD: I'm going to double back really quickly, because you mentioned in the inguinal nodes doing endoscopic surgery. So for us non-surgeons maybe to explain. So we're used to thinking about open surgeries or laparoscopic surgeries, what is an endoscopic surgery in a groin?

Anthony Visioni, MD: It's synonymous with laparoscopic surgery? The only difference being laparoscopic truly is abdominal surgery. Endoscopic, most people would think about flexible endoscopes, but it's not quite that either. So it becomes a surgery where we don't have a name for it, quite frankly. So technically what we often call it is a veil a V-E-I-L a Video assisted Endoscopic Inguinal Lymphadenectomy because everything has to have a fun acronym these days, right? So this is a procedure where I use all of the equipment of a laparoscopic surgery, but instead of insufflating CO2 into the belly to develop a working space, actually insufflate the thigh, and I can get enough working space to then dissect along the borders of a lymphadenectomy that we need to dissect and safely remove those lymph nodes off of the femoral vessels. And to do what should be a very clean and very thorough removal of those lymphatic lymph nodes that would be synonymous with an open surgery.

Dale Shepard, MD, PhD:And certainly when you do the inguinal nodes, we talked before about lymphedema and problems that happen. So you talked about the endoscopic surgery in the groin helping out from a wound perspective. Do we also get a similar benefit from a decrease in lymphedema?

Anthony Visioni, MD:No, unfortunately we don't. And it's because of really the underlying etiology of that lymphedema is the trauma and the removal of the lymph nodes. So if you're doing the correct operation, unfortunately you're going to have the same rates of lymphedema. But that being said, when you have decreased wound complications, it could get patients on to faster treatment for lymphedema, if they need to have bypasses or lymphaticovenous bypasses, those things can be generated a little bit quicker, hopefully. And just not having those wounds is just from a patient perspective, much easier to deal with and increases the satisfaction from that perspective as well.

Dale Shepard, MD, PhD: That's great. Are there any advances in imaging, for instance? Or any other areas that help you out from a surgical standpoint?

Anthony Visioni, MD: Yeah. So one of the hallmarks of melanoma has been probably still always will be lymphoscintigraphy. So sentinel node biopsy is pretty well known, particularly in the field of breast cancer. Breast cancer, generally speaking, can only go to your axilla. So we don't have to do preoperative imaging to, to identify our lymph node basins, but in melanoma that's pretty well required. What's interesting though, is as we're learning new techniques about identifying lymph nodes, one of the things that actually some of the work done here at Cleveland Clinic has shown is injection of a tracer called Indocyanine green and using near infrared light can identify those lymph nodes quite well in the operating room after lymphoscintigraphy. And that may actually provide better staging for patients because we can see the lymph nodes better, more accurately dissect them, potentially reduce the risk of outside trauma around those as well.

So I think that's something that I think will be gaining traction, not just here, which I have an interest in. I know Dr. Gasman at the main campus has an interest in, but particularly around the country. I feel like that's an area that even something as fundamental as a sentinel lymph node biopsy may see some changes.

Dale Shepard, MD, PhD: So lots of change. Changes in imaging, changes in where we use our systemic therapies, surgical techniques, lots of exciting things going on. What else is out there? What's the biggest gap? So when you think about how you treat patients, what's the biggest thing you'd like to be the next thing to change? What's the biggest barrier to progress?

Anthony Visioni, MD: Yeah, I think that's a brilliant question because I think there is a fairly looming gap and it's something as fundamental as better stratifying these techniques and these pathways of care. So melanoma, as I kind of mentioned earlier is a very straightforward disease, but there's so many curve balls to it. So it is a disease that will find ways to trick you and find ways to cause problems down the road. The vast majority of patients with melanoma will actually present with a fairly early stage, highly curable disease, but it's the nuance of who is not going to be that patient that we're still trying to figure out. And our AJCC staging does fairly well, but I don't think that's a really nuanced enough guideline or nuanced enough protocol to follow, to know how to implement the best treatments for these patients. So to that end, I think one of the gaps is really figuring out a little bit more of the biology of melanoma intrinsically and being able to molecularly stage, so to speak, some patients to then know who to bring to bear the most aggressive treatments or who we can dial back some of these very expensive treatments. And even though they are less toxic, they're not non-toxic. So I think that's a really big gap going forward that I would love to see filled. And actually, I think that there's some really good studies looking at that as well.

Dale Shepard, MD, PhD: Considering we're talking about melanoma and you mentioned curveballs, I'm going to have to throw you one, right? So the easiest disease to treat is the one you don't need to treat. And so how do we do a better job of not getting to the stage where we have to treat this disease at all? We know sunscreen's helpful. We know that early detection is helpful. And we get the message out. How do we, how do we do a better job on the, way on the front end? We have all this time and energy on these late stage therapies. How do we work on the back end and just minimize the numbers?

Anthony Visioni, MD: Yeah, that's absolutely right. I'd say, the number may vary a little bit, but it's well over 90% of melanoma, we attributed to UV exposure and that in general is sun exposure, right? So I think the first thing that we can really address is tanning beds and, quite frankly, making sure that those are better regulated and more information is given to the users of tanning beds to understand what is happening. I am a firm believer that really teens should never be in a tanning bed. Obviously, I come from a fairly biased, but I think reasonable perspective on that. And, quite frankly, I don't know if my bias may extend so far as to say, I view it very much like there's no good tanning bed, right? So there's no low-risk tanning bed. And I don't think that they should be used. So if we address that, I think that's one point of things, but then it is more informational.

So I do remember even when I was a kid, you wouldn't go and put sunscreen all over yourself. And if anything, my wife and other people I know would actually try and put like baby oil on and get a tan. So it's really that education I think is, is started and improving. But it's to continue to do that in both the primary care office, when they may never see a specialist, as well as things like a barbershop. So barbers are constantly looking at a patient's scalp, their upper back and neck, and even just knowing that barbers can disseminate some of this information too. We actually find quite a few scalp melanomas from barbers. And so having really community involvement in this kind of process is hugely important.

Dale Shepard, MD, PhD: That's great. Well, I appreciate all the work you're doing for patients with melanoma. You've had some great insights here and I appreciate you joining us.

Anthony Visioni, MD: Thank you so much. It's such a pleasure.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget you can access real-time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.