BTK Melanoma Clinical Challenges v2
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Speaker: [00:00:00] Hi, everyone. Welcome back to another episode with your Behind the Knife surgical oncology team. Let's get started with quick reintroductions. I'm Joe Broderick. I'm a research resident at Brooke Army Medical Center. I'm Galen Giss. I am

Speaker 2: a research resident as well at Brooke Army.

Speaker 3: Hi, I'm Elizabeth Barbera.

I'm a general surgeon at RAF Lakenheath in the UK. I'm Lexi Adams.

Speaker 4: I'm a surgical oncology fellow at MD Anderson.

Speaker 5: Tim Brila. I'm a surgical oncologist at

Speaker: Brooke Army Medical Center. Okay, let's get started. Today, we're discussing clinical challenges in melanoma. Melanoma management has changed dramatically over the last decade.

It's become one of the best examples of how surgical decision-making requires a truly multidisciplinary approach that integrates pathology, imaging, advances in systemic therapy, and evolving clinical trial data. For general surgery residents, these patients can be deceptively complex, from deciding who needs a sentinel lymph node biopsy to managing nodal disease to understanding when surgery actually helps and when it may add morbidity without improving outcomes.

So [00:01:00] today, we're walking through some of the most common and highest-yield clinical scenarios you'll likely encounter. Beth, you think you could get us started?

Speaker 3: Sure thing. So Galen, we have a forty-five-year-old female. She's referred to your clinic for a pigmented lesion on her forearm. Her PCM's worried that the lesion might be melanoma.

How would you start your workup?

Speaker 2: Yeah. Thanks, Beth. I'd start by obtaining a history and physical, focusing on family history, timing of the lesion development, any changes that have been noticed in the specific lesion. I'd also perform a complete skin exam and then a focus exam on the lesion in question, along with the draining nodal basins.

To obtain a proper diagnosis, I'd obtain a full thickness biopsy of the lesion.

Speaker 5: Okay, so Galen, you mentioned the key aspect was, which is to get a full thickness biopsy. So there's a couple ways to do that. Punch biopsy is usually the easiest. You're gonna get somewhere three, two, three, four-millimeter punch, whatever it may be, and then you can just put a stitch to close that, and then you know it's not gonna heal great, but whatever, you're gonna [00:02:00] excise it again later.

The reality is that a lot of these patients are getting biopsied before they come to you, and the hard thing is that they're not gonna get full thickness biopsies. So a lot of dermatologists, because the reason that they don't get punch biopsies elsewhere is 'cause the punch biopsy usually doesn't excise the lesion, and that's what the patient really wants.

They want the lesion gone, and they don't fully realize the implication. So they do a shave biopsy to get rid of it, and then, oh, it came back melanoma. Oops. And so you'll get this shave biopsy pathology report, and what's the most important thing on your pathology re-report when it comes back invasive melanoma?

It'd be the depth. Yeah, the depth, and so that's the problem. And if you get a shave and then the deep margin is positive, and now you as the surgeon are stuck with, "I don't really know how deep this goes," and so you hope that they at least got it deep enough that your surgical decision-making isn't gonna be affected But, you know, [00:03:00] reality is your preference is always gonna be a full thickness biopsy, which means going down to the subcutaneous fat because then you know for sure that you're gonna get the, the depth of the lesion.

You can do that with an excisional biopsy or you can do it with a punch. It's just easier to do a punch most of the time 'cause it's a small hole, it's easy to close. You can always come back and excise the rest if it comes back as something benign. You guys may talk about an excisional biopsy. I think excisional biopsy is generally not the right answer.

If you end up taking a little bigger margin than you want, and then you have to do an ellipse to get it to close, you could screw up the lymphatics and throw your sentinel node off later. There's just no reason to do that. If you are suspicious of melanoma, you need a full thickness biopsy. Punch biopsy is the most efficient way to do that.

Speaker 3: Okay, great. Thanks, Dr. Vreeland. Let's go back to our case for a little bit. So let's say the patient has no significant family history of cancer. She first noticed the lesion a year ago. Over the past six months, the lesion has grown slightly, and she occasionally notices a [00:04:00] small amount of bleeding. On examination, you identify a one centimeter lesion on the right forearm with scattered pigmentation, irregular borders, and ulceration.

There are no abnormal nodes identified on exam. Final pathology from your biopsy demonstrates malignant melanoma with a Breslow depth of one point five millimeters. Is there any additional staging we need to do before proceeding with treatment?

Speaker 2: With an otherwise normal complete skin exam, no palpable nodes, no symptoms that are concerning for metastases, we don't need any additional staging at this time.

If she had palpable lymphadenopathy, then I would get an ultrasound with a possible biopsy of that nodal basin.

Speaker 3: Okay. So again, this patient did not have any palpable lymphadenopathy, so you don't need an ultrasound. How would you proceed with treating the patient?

Speaker 2: So for a patient with a Breslow depth of one point five millimeters and clinically node-negative disease, I'd offer a wide local excision with a sentinel lymph node biopsy.

Speaker 3: Okay. So can you talk us through your decision to perform a sentinel lymph node biopsy? [00:05:00]

Speaker 2: Definitely. So in clinically node-negative melanoma, we generally think about three groups based on Breslow depth and ulceration. So first, for lesions that are less than point eight millimeters without ulceration, the probability of a positive sentinel lymph node is less than five percent.

Therefore, sentinel lymph node biopsy can be generally deferred. Second, for lesions less than point eight millimeters w- but with ulceration or lesions point eight to one millimeter with or without ulceration, the risk of a positive sentinel lymph node increases to five to ten percent. Therefore, sentinel lymph node biopsy should be considered.

And then lastly, for all lesions greater than one millimeter, the risk of positive sentinel lymph node biopsy is greater than ten percent, and therefore, sentinel lymph node biopsy should be performed. It's important to keep in mind that these are general guidelines for cutaneous melanoma, but you should be aware that these can change based on the type, locations, and other melanoma risk factors.

Speaker 3: So in summary, for clinically no- negative melanoma patients, a sentinel lymph node biopsy can [00:06:00] generally be deferred in those with lesions that are less than point eight millimeters without ulceration. If the lesion's greater than, uh, or equal to zero point eight millimeters or if it's ulcerated, sentinel lymph node biopsy is generally recommended.

Additionally, it's worth noting that a sentinel lymph node biopsy is a staging procedure, and margin cutoff recommendations are based on risk-stratified cohorts used to estimate the likelihood of more advanced disease. Remember, a sentinel lymph node biopsy alone does not confer a survival benefit. Okay, Galen, can you briefly discuss resection margins for us?

Speaker 2: Definitely. So in general, lesions with a Breslow depth up to one millimeter need a one centimeter margin. Lesions between one to two millimeters require a one to two centimeter resection margin. And lastly, lesions over two millimeters need a two centimeter resection margin. So this patient with a Breslow depth of one point five millimeters would need a one to two centimeter resection margin.

Yeah, just, uh,

Speaker 5: margins are pretty simple. [00:07:00] I just say multiply the depth by ten, that's your margin. So you're never gonna do less than a centimeter, you're never gonna do more than two centimeters. There was a study that looked at two versus four for larger melanomas, and it made no difference, so you cut off at two, and then you're always gonna do a centimeter for an invasive melanoma, and then just multiply it by ten.

There is an ongoing study right now looking at those one to two millimeter T2 melanomas and looking at one versus two centimeters, so hopefully we'll have an answer, a miranda-- randomized trial at some point there. The guidelines kinda talk about cosmetically sensitive areas, you can do one centimeter, so it's just easy to multiply by ten and do that.

So if one point five millimeters, I would just do one point five centimeters. To make the nodal or the sentinel node discussion a little more complicated, in your guys' career in the next five to ten years, these things will probably hit guidelines, but there are now essentially kind of like an oncotype DX study for [00:08:00] these.

So there are a couple commercially available tests that will go deeper into the molecular analysis of the specimen and try to tell you how high risk this patient is. So one of them is designed to tell you that T2 tumors do not need a sentinel node biopsy, and then the other one is designed to tell you smaller T1 tumors that they do need a sentinel node biopsy.

There's gonna be more of those commercially available, and at some point, they're not exactly standard of care right now. Most people are just using the guidelines, but be aware that those tests are out there and probably will be prime time in the next five years or so.

Speaker 3: Okay, awesome. Great to know that those things are coming down the pipeline.

So Galen, you perform your wide local excision and your sentinel lymph node biopsy. You have a margin of one centimeter, and your nodal biopsy shows isolated melanoma cells For the positive sentinel lymph node, do you need to perform a completion lymph node dissection?

Speaker 2: Okay, so my margins are adequate, but I have one positive sentinel lymph node.

However, [00:09:00] even with one sentinel lymph node, a completion lymph node dissection is generally not needed. Joe, can you briefly remind us of the MSLT2 trial and its findings regarding completion lymph node dissections?

Speaker: Yeah, definitely. MSLT2 was a multicenter Phase III randomized controlled trial in patients with up to three positive sentinel lymph nodes comparing immediate completion lymph node dissection with nodal observation using ultrasound surveillance.

They demonstrated no melanoma-specific survival benefit to completion lymph node dissection, though there was some improved regional control. As a result, the NCCN recommends active nodal basin surveillance over completion lymph node dissection for most clinically node-negative patients found to have positive sentinel lymph nodes.

Speaker 3: Okay. Thanks, Joe. So Galen, how often are we performing these surveillance ultrasounds, and is this patient going to need systemic therapy?

Speaker 2: That's a great question, Beth. As far as nodal ultrasounds go, every three to four months for the first two years, then every [00:10:00] six months through year five. For patients with a positive sentinel lymph node, they should all be considered for systemic therapy.

Speaker 5: Just to add a couple little things. MSLT2 was one of these major studies paradigm shift in the treatment because everybody with a positive node used to get completion node dissection no longer get that. That does not mean that those patients would not have had additional positive nodes. So in the dissection arm, I think thirty percent of patients had additional positive microscopic nodes.

And so what happens to those patients, right? They're-- The difference is that their melanoma-specific survival didn't change with the ax dissection, and a lot of them did recur clinically later and then get an ax dissection later. But the idea is you're gonna save seventy, eighty percent of patients within the first five years, I think was the initial publication, from an axillary dissection or even worse in melanoma is a groin dissection, right?

So ax dissection, the [00:11:00] morbidity, eh, sure, there's some morbidity. But groin dissections, especially in America where many patients are obese, is extremely morbid. The wound complications, the wounds all fall apart, and lymphedema in addition. So that's the thing you have to think about differently with, with melanoma than breast, is that you're not just talking about axillary dissections, but you're also lumping in groin dissections, which are much more morbid.

So this study told us seventy percent of patients probably can avoid a completion dissection, so let's go ahead and avoid it in those patients, and we'll watch them closely, and then if they recur, we'll operate. The other really important thing to remember is that this trial was done With no adjuvant therapy.

So the whole world of melanoma has changed since this trial was published because now there's adjuvant therapy. And so we're doing even less completion dissections because patients are getting adjuvant therapy, and we'll talk about that a little bit here. The other key point that I don't know if mentioned, was mentioned is this is only for [00:12:00] clinically node negative.

So I think some people get confused there. On their boards or on their oral boards, they'll get a patient with a clinically positive node, and then they'll try to apply MSLT2. This only applies to patients who are clinically node negative up front.

Speaker 3: Those are all really great points. Thanks, Dr. Vreeland.

Okay, let's shift our focus onto the management strategies for different nodal basins. Lexi, can you take it away?

Speaker 4: Yeah. Sure thing. So Joe, you have a patient presenting with melanoma now on their right mid back with a Breslow depth of one point five millimeters and otherwise has an unremarkable physical exam.

So like in our last patient, this patient will need a sentinel lymph node biopsy, but how do we n- manage the nodal basins in this patient?

Speaker: Yeah. So patients with truncal lesions require bilateral cervical axillary and inguinal lymph node basin examinations. And then with no palpable nodes on exam, this patient will require preoperative lymphoscintigraphy to determine the drainage pattern for this lesion.

Speaker 4: Yeah, that's right. So patients with truncal melanoma, they can have complex [00:13:00] lymphatic drainage, and they should be evaluated preoperatively with lymphoscintigraphy. Can you remind us what that is and how we do it?

Speaker: Yeah, definitely. Lymphoscintigraphy is a nuclear medicine study that uses radioactive tracers to visualize the lymphatic system.

You basically inject a small amount of tracer into the skin around the biopsy site, usually the day before or the day of surgery, and then you use a gamma camera to track the tracer as it travels through the lymphatic system. You can take both static and dynamic pictures of the area to determine the primary draining basins.

And then in the operating room, you use a handheld gamma probe, usually combined with a blue dye, to localize or remove the nodes for staging.

Speaker 4: Exactly. So in this patient, you perform lymphoscintigraphy, and it shows drainage to the right axilla and the right groin. Well, what do you do with those findings?

Speaker: Yeah. So this patient will require a sentinel lymph node biopsy in both the axilla and the groin. In each lymph node basin, the node with the highest gamma count is removed along with all nodes with gamma counts greater than ten percent of the [00:14:00] highest sentinel lymph node.

Speaker 5: Yeah. So just important to know that you'd wanna gather that information before you get to the operating room because especially with a melanoma on the back, you often have to flip the patient, reposition, and you just don't wanna do all that and then find out you have to do something different.

The other thing, you said blue dye, extrapolating from breast, this all works better with two types of dye. The other kind of cool thing that's out there now is ICG with spy, so you can inject intradermal ICG and then use a spy to find the nodes. And so I'm often doing all three right now just to get used to using the ICG, but it, it's pretty cool.

Speaker 4: Yeah. Thanks, Dr. Breland. So each lymph node basin identified in lymphoscintigraphy requires its own sentinel lymph node biopsy. So let's now discuss how we manage palpable nodal disease. So if we take our patient from before who had melanoma on their forearm and a Breslow depth of one point five millimeters, but now they have a firm palpable node that you feel on exam of their axilla, now how would you proceed, Joe?[00:15:00]

Speaker: In a patient with a clinically palpable node, I'd move forward with an ultrasound of the nodal basin, including her epitrochlear nodes, as well as a biopsy, leaving a marker for later identification. I'd also perform BRAF testing, as patients with nodal disease and BRAF mutations can receive targeted systemic therapy with BRAF inhibitors.

Speaker 4: Okay. So you get an ultrasound, and it shows a single regular node in the axilla and no epitrochlear nodes. Biopsy confirms it's melanoma, and it's BRAF negative. How would you move forward now?

Speaker: For a patient with resectable stage III melanoma with a single biopsy-proven nodal metastasis, I'd recommend neoadjuvant immunotherapy followed by resection of the primary, if still present, and a therapeutic axillary lymph node dissection.

Speaker 4: All right, great. And quick side note, BRAF testing can be important to determine different targeted therapies, but it should be remembered that regardless of BRAF status, immunotherapy is still their first-line therapy. So targeted BRAF/MEK therapy [00:16:00] is reserved for if they fail immunotherapy for some reason or they have recurrence or metastatic disease down the line.

So, Galen, can you remind us why we're doing neoadjuvant immunotherapy instead of just upfront resection?

Speaker 2: Definitely. This is based on the NADINA trial, which we discussed in our last episode, which showed that in patients with resectable macroscopic clinically node-positive melanoma, receiving two cycles of neoadjuvant immunotherapy demonstrated a twelve-month event-free survival of eighty-three point seven percent as compared to those who did not receive neoadjuvant therapy and underwent an upfront therapeutic lymph node dissection, who had an event-free survival of fifty-seven point two percent.

Speaker 4: Thanks, Galen. So now, Joe, tell us about the approach to managing nodal disease.

Speaker: Yeah. The NCCN guidelines recommend an anatomically complete dissection of the involved nodal basin. So for the axilla, a dissection's historically included levels one through three. However, the [00:17:00] need for a routine level-three dissection has not clearly been defined in the modern era of systemic therapy.

This is an important distinction for breast cancer, where an axillary lymph node dissection more commonly refers to levels one and two and not level three.

Speaker 4: Great point. So while in breast cancer we only dissect lateral and inferior and deep to the pec minor for a level I and II dissection, in melanoma, we also have to dissect medial and superior to the pec minor to access the level III nodes

Speaker 5: Yeah.

One key thing that was mentioned is that neoadjuvant actually has a survival benefit for node-positive patients. So where we will probably head is that we'll get ultrasounds on everybody upfront, just like we do for breast because one problem is physical exam is not that reliable, particularly in obese patients.

And so this came up in breast, what? Five, six, eight years ago. How do we define clinically node-positive? Clin- the old-school answer, clinically node-positive meant you could feel the [00:18:00] lymph node, but then we started ultrasounding everybody, and now you have these patients with non-palpable nodes that are positive on ultrasound and biopsy-positive.

Are they clinically node-positive? Do they need an, a completion dissection? Uh, you know, everything's changed around that with targeted dissection in breast, but you're almost certainly missing some clinically node-positive patients if you're just using physical exam. Unless they're, you know, really thin, and even then, if you have a microscopically positive node where it has a thickened cortex on ultrasound but not enough for you to feel it, do you wanna find those patients?

And so that's where I think currently it's a little bit in flux. But if you have a T-three patient, no palpable nodes, I would say that you should be getting an ultrasound of the nearest lymph node basin or maybe a couple lymph node basins if they're truncal like we talked about. But y- the paradigm shift is that now I actually really wanna know if there's a positive lymph node upfront because then I can totally change my treatment paradigm, give neoadjuvant, and then arguably [00:19:00] maybe avoid a completion dissection depending on how mature you want the data to be before you start doing that.

We talked about last time some phase two data that if you have a strong pathologic response to neoadjuvant immunotherapy, that maybe you can avoid a completion dissection in that setting. And so if we get to that point where everybody with a clinically node-positive upfront is getting immunotherapy, and then some percentage of them are avoiding a completion dissection at the end, then I would argue you should really be searching to find those positive nodes upfront.

Speaker 4: Thanks, Dr. Breland. We resect the primary lesion, perform a therapeutic lymph node dissection, and then the patient goes on to their adjuvant immunotherapy.

Speaker 5: Yeah, just a comment there, right? Because some of that depends on the path, right? So if the patient gets upfront immunotherapy, and then you do- Right

your completion dissection, and they have a past CR, they may get nothing post-surgery, or they [00:20:00] may get less immunotherapy. So, uh, all this stuff is changing, and by the time some of you guys are out and about, it'll have changed again. But just be aware that part of the reason you're doing that lymph node dissection is really just to get a pathologic assessment of their medical therapy.

And so their adjuvant, their post-op therapy really will flex depending what you find in the operating room.

Speaker 4: All right, great. So Beth, do you wanna take the next case?

Speaker 3: Yeah, absolutely, Lexi. So Joe, we have a similar scenario as before, except now the patient has a primary lesion on the thigh with palpable nodal disease in the groin.

How do you manage the nodal disease here?

Speaker: For a patient with palpable nodal disease in the groin, I would get a CT or MRI of the pelvis to evaluate deeper iliac and obturator lymph nodes for disease. Then if these were negative, I would perform inguinal femoro lymph node dissection. However, it's worth noting that clinically positive inguinal femoro lymph nodes increase the likelihood of a occult external iliac or obturator [00:21:00] microscopic disease, as does three or more microscopically positive superficial nodes or a positive cloaca node.

In these settings, a deeper dissection should be considered. So

Speaker 5: we're talking about a groin dissection. All the appropriate caveats, right? Like give immunotherapy first. Do adequate imaging first. I would get a PAT as well. One of my mentors used to say, when we're talking about groin dissection, I'm sort of looking for a reason not to do it, but you can help some patients by doing a groin dissection, so be prepared to do it.

But what you don't wanna do is go do a groin dissection, wound complications, morbidity, lymphedema, and then they have an, an internal iliac or a, a aortic chain node positive three months later, something like that, right? So look hard for those higher nodes because to your point, they very well may be there.

And then the controversy of when to do a superficial and deep, they're-- these answers are tough. So the cloaca node is kind of the classic thing, [00:22:00] but in practice it's not always very helpful. So if you have any inclination that the deep nodes are positive, you're gonna do a superficial and deep. One of the issues there is that frozen section in most centers is not possible because it's really hard to tell a melanoma cell from a lymphocyte on, on a basic stain.

They have-- That's why like they're always talking about the melanin stain on the path, and most centers are not gonna do that as a frozen. So you can't use your frozen to make that decision, so you typically have to make that decision before you get to the operating room. The other interesting thing about groin dissection is what incision to make.

So that's become kind of an area of controversy. So the old school answer was this lazy S where the more transverse part was on the inguinal ligament, but a lot of people now are doing two separate incisions. So they do kind of a superficial groin dissection incision below the inguinal ligament and then kind of a kidney transplant incision above the inguinal ligament, and do it as two separate, almost two [00:23:00] separate surgeries, but you connect across the inguinal ligament to make sure you get all the lymphatic tissue.

The reason being because that lazy S, it crossed the groin crease, and the groin crease, it's just impossible to get anything to heal in the groin crease. And so using that two separate incisions and trying to keep both of them out of the groin crease decreases the wound morbidity somewhat

Speaker 4: Yeah, these groin dissection incisions can be extremely morbid.

I know my month on melanoma, like three-quarters of my patients came back with groin wound complications needing dressing changes, wound VACs, et cetera. And we've even started doing minimally invasive incisions, which really decreases the wound burden. They still might come back with drain complications or ser- infected seromas, but it does really decrease the amount of wound

Speaker 3: morbidity.

Thanks, Dr. Vreeland and Lexi for those points. I think those are really important aspects to bring up. So Galen, what if the patient presents with a primary lesion on the cheek? Let's do something different.

Speaker 2: Okay. [00:24:00] So for primary head and neck melanomas, they can have complex lymphatic drainage to both the parotid and neck lymph node basins.

So if they have clinically involved nodes in the parotid or the neck, management generally includes consideration for superficial parotidectomy, possibly with facial nerve preservation when indicated, along with appropriate therapeutic neck dissection. So with that being the case, I would want to get ENT involved as well as possibly plastics for reconstruction.

Speaker 5: One inter- interesting thing about all this stuff about morbidity of dissections in melanoma is that most of these trials did not include head and neck melanomas specifically because there's no such thing as lymphedema of the head. So the morbidity of a neck dissection is the incision is sometimes not cosmetically great, and you can have nerve injuries, but you don't worry about lymphedema.

And neck wounds tend to heal very well too. But yeah, neck dissections are so rare now, we just don't do a lot of them, and so I think it'd be reasonable to involve ENT if you have an ENT that's comfortable with them, right? 'Cause even the ENTs aren't [00:25:00] doing it that often.

Speaker 4: Yeah, and as a quick side note, if they do have a small lesion and they don't have palpable nodal disease, some may consider Mohs surgery, which could improve cosmesis, but you'd have to go to a, a local Mohs surgeon for that, and that is not technically in the guidelines.

Speaker 5: So in practice, people are doing it, but the guidelines would never say to do that, would never say that on my oral boards. And Lexi and I are involved with the COC Cancer Standards, and it's one of the major issues with the melanoma standard is that the standard very clearly says that you do not use Mohs, and there's dermatologists treating melanoma and treating it with Mohs.

And so by COC standards, by NCCN guidelines, that is not a, a standard way to treat invasive melanoma.

Speaker 4: Thanks, Dr. Vreeland. Let's walk through one more scenario that's somewhat unique to melanoma. So Joe, a patient presents with a forearm lesion and a palpable axillary node like before, but he also has another lesion on his upper arm.

What would you call this lesion? [00:26:00]

Speaker: This likely represents an in transit lesion, which is a manifestation of intra-lymphatic tumor spread. There are several terms for intra-lymphatic tumor spread, satellite, microsatellite, and in transit disease based on the lesion's relationship to the primary tumor These lesions occur within dermal or subdermal lymphatics between the primary tumor and the draining node basin, and carry a similar prognosis as macroscopic nodal spread.

Galen, can you tell us about how they are treated?

Speaker 4: Yeah. And just to quickly define some of those terms. So an in-transit lesion would be a lesion greater than two centimeters away from the primary, whereas a satellite lesion would be less than two centimeters away. Microsatellite lesion is not one you see on physical exam, but instead one, a lesion you see under the microscope on your pathology specimen.

Speaker 2: Thanks, Lexi. So this is where melanoma treatment can start getting pretty complicated. So for the purposes of today, if a patient has otherwise resectable disease, these lesions can also be resected. Unlike the primary lesion, however, these [00:27:00] in-transit lesions or satellite lesions only need to be resected to histologically clear margins.

Speaker 5: Yeah, there are some other therapies available for these, but unfortunately nothing works great at this point. But some combination of the immunotherapy, there are injectable therapies. There's a T-vac, which is a herpes virus derivative that can be injected directly into the lesions and can help. And so you're right, it gets very complicated at that point.

There's isolated limb perfusion, things like this that we don't do a whole lot. But and just for any surg onc fellows out there, this was one of my questions on my oral boards for surgical oncology because it is very complicated and they like kept pushing you to go through every option. So there's a lot out there.

Speaker 4: So Joe, can you follow up more generally on what the follow-up should look like for these patients?

Speaker: Yeah. Follow-up varies by stage, but patients are generally seen for a history and physical every three to six months early on, and then less frequently over time, with imaging guided by symptoms and risk.

Speaker 4: [00:28:00] So we've now covered a variety of presentations for resectable nodal melanoma. It's also worth noting that these guidelines may change after the results of the ongoing MSLT-3 trial. So Galen, can you briefly discuss the background for this trial?

Speaker 2: Yeah. This trial is part of what Dr. Veenland was talking about earlier, and it's MSLT-3, which is follow on to PRADO, which we discussed in our last episode.

In brief, PRADO is a single-arm phase II trial investigating the feasibility of using the index lymph node, the largest lymph node in the lymph node basin, to guide management of patients with macroscopic clinically node-positive melanoma after receiving neoadjuvant immunotherapy. All patients underwent marking of the index lymph node at enrollment, followed by two cycles of neoadjuvant immunotherapy with index lymph node resection at week six.

And as Dr. Veenland was talking about, the completion lymph node dissection or adjuvant treatments based off what they found on pathology of the index lymph node. Patients who had a major pathologic response in their index lymph node did not [00:29:00] undergo a subsequent therapeutic lymph node dissection or adjuvant immunotherapy, and they had a twenty-four-month recurrence-free survival of ninety-three percent, a distant metastasis-free survival of ninety-eight percent.

This was a single-arm study with a small sample size. However, this is where MSLT comes in. Betts, can you take it from here?

Speaker 3: Yeah. So this trial is really important because we're actually investigating de-escalation of treatment. MSLT-III is a phase III randomized control study. This aims to answer the question of whether or not it's truly safe to de-escalate therapy based on the pathologic response in the index lymph node.

So using a similar cohort as the PERDTO trial, patients with macroscopic nodal melanoma will receive neoadjuvant ipilimumab and nivolumab, undergo index lymph node resection, and those with a major pathologic response will be randomized to either a total lymph node dissection or surveillance. The results of this study will hopefully tell us if patients who have a major pathologic response really need to undergo a total lymph [00:30:00] node dissection, as well as the risks of its associated complications.

Speaker 5: Yeah, I think that's the big trial everybody's gonna wait for. Unfortunately, it just started enrolling not too long ago, so it's probably years away from being resulted out. But I think we're in this kinda tough area right now. Should you be offering the patients a more limited dissection based on PERDTO, given that it was a phase II single arm?

There's no randomized trial. It's not gonna hit the guidelines. So everybody's waiting for MSLT-III. My suspicion is that it will show that a completion node dissection is not important in those patients that have a major pathologic response, just like MADINA, but we're just not there yet. So for now, the standard is still to do a completion dissection, so that's what I would answer on my oral boards.

Again, that's for clinically node-positive patients. Clinically node-negative patients who have a positive sentinel node should not get a completion dissection based on MSLT-II. Thanks, Dr. Vreeland.

Speaker: So we've covered a [00:31:00] lot today, but let's try to sum it up. Patients with suspected melanoma should undergo a full skin examination, evaluation of the draining nodal basins, and a full thickness biopsy of the lesion.

If they don't have evidence of regional distance spread, they can undergo a wide local excision and require a sentinel lympho biopsy if the lesion is greater than point eight millimeters or has ulceration. The patient of the truncal lesion or any other lesion with ambiguous lymphatic drainage, preoperative lymphoscintigraphy is essential to determine the correct nodal basin for sentinel node and sampling.

Patients with palpable lymphadenopathy should receive neoadjuvant immunotherapy and a therapeutic lymph node dissection followed by adjuvant therapy, while patients with only sentinel lymph node positivity can undergo ultrasound surveillance without a therapeutic lymph node dissection, but typically still require adjuvant therapy as well.

Each nodal basin has its own unique management principles, and patients should be monitored carefully postoperatively for recurrence. Lastly, the ongoing MSLT-III trial may further shift the [00:32:00] paradigm of nodal management by determining whether patients with a major pathological response in the index lymph node can safely forgo therapeutic lymph node dissection.

I think that's it for today. Thanks for joining us on Behind the Knife Surgical Oncology. Dominate the day