Treatment Advances for Advanced Melanoma - Episode 2
Axel Hauschild, MD: The question is, what do we do with patients if the sentinel node is positive? Do we need a completion lymphadenectomy? I guess it’s very important to emphasize that the patients who have macrometastasis, palpable lymph nodes, nodes seen in the lymph node sonography, or in CT or MRI scanning, will be resected anyway with the completion of lymphadenectomy. That’s not the issue. It’s the tiny, positive sentinel node. We question if we need a completion lymphadenectomy. This is particularly being discovered in MSLT-II and in a German study. Mike, what is your gut feeling about the data? Is this changing the rules in your center.
Michael A. Davies, MD, PhD: Again, it’s part of the transformation we’re seeing in the care of melanoma patients. We’ll talk about the adjuvant therapy trials that have been completed, and we have to remember that those trials were completed in the era when patients were all getting completion lymph node dissection. We’re moving into an era that offers adjuvant therapies to patients who are undergoing sentinel lymph node biopsy without a completion lymph node dissection. I think we’re all going to be looking at how that sort of affects the risks of local and regional relapses. But absolutely, it’s very standard for us to do the sentinel lymph node biopsy. I would reinforce the idea for the patient who presents with a site that is 1 mm or thicker, but there are certainly considerations for patients with thinner melanomas but with high-risk features. Certainly, ulceration.
I think the other thing that’s good to remember is the signs of regression. With regression, you don’t actually know what the original Breslow thickness was. That’s something else that we look at when we’re talking about whether to do the sentinel lymph node biopsy. But you’re right, and I agree with the other panelists. It’s very unusual for us to do a completion lymph node dissection after a positive sentinel lymph node biopsy.
Merrick I. Ross, MD: So Axel, I think there are some things that we need to talk about. Even though most people would consider the sentinel lymph node biopsy as a staging procedure, the completion lymph node dissection trials in Europe and in the United States show that there was no survival advantage. But those trials also showed us that the patients who have additional positive nodes are a different biology than patients with disease limited to the sentinel lymph node.
Even though we used to think that sentinel lymph node biopsy was just a staging procedure, the MSLT-1 data would show us that removing the sentinel lymph node, particularly if that was the site of disease in the nodes, was actually therapeutic. There’s a survival advantage for the node-positive patients compared with patients who develop clinical nodal disease. So the MSLT-1 trial did show us that there are some survival advantages by removing the disease early. So the concept of removing lymph node disease early has actually been proven as having an impact on outcome.
The completion lymph node dissection doesn’t provide any additional advantage in terms of overall survival and provides only improved regional disease control and, possibly, some information related to staging. There may be other surrogates for outcome that you may not have for the staging information to make decisions about adjuvant therapy. The burden of disease in the sentinel lymph node may be a very important piece of information that helps our medical oncology colleagues make decisions about adjuvant therapy, so we may not even need to do the completion node dissection to get the staging information.
Axel Hauschild, MD: So your conclusion is: It adds some prognostic information. It’s a very sensitive tool for evaluating whether patients are candidates for adjuvant treatment in the future, and we will touch on this later. And also, it has some therapeutic implication but only with the sentinel node staging.
Merrick I. Ross, MD: Correct.
Axel Hauschild, MD: Is this affecting your guidelines in the United States and in France? In Germany, we will have a discussion in the upcoming months. If a German study has been published, the rule is that we can discuss fully published manuscripts only for changing guidelines. I can tell you that it will be a tough discussion in Germany—if we proceed with completion lymphadenectomy for sentinel node-positive patients in the light of 2 negative large-size randomized clinical trials.
Merrick I. Ross, MD: The [National Comprehensive Cancer Network] guidelines in the United States are about to publish based on a meeting from June. Certainly, the omission of completion lymph node dissection will be part of the guidelines as an option for patients and surgeons. There will also be an option to discuss completion lymph node dissection with patients as well. The guidelines are changing, and I think surgeons in the United States have adopted this change and this transformation.
I think it’s very important to remember where we came from and how much progress we’ve made. I’ve been treating melanoma for 30 years, and the disease that we see is very different. A lot of that has to do with early diagnosis, but it also has to do with early diagnosis of nodal disease.
We don’t see gross nodal disease as much as we used to. I think sentinel lymph node biopsy has been important in changing how patients present with more advanced cases. That’s a good thing, and the staging system actually reflects this. The stage I and II patient population does better based on stage migration because we’ve moved the early stage III patients into the next group. The stage III patients do better because they’re mostly microscopic node positive.
Axel Hauschild, MD: We covered the field of surgery, but do you think that surgery, in the future, will have a different role because adjuvant treatment, which is coming up and was recently approved in Europe and in the United States, is relatively strong? Is there a role for surgery in patients with 3 positive sentinel nodes when we know that the adjuvant treatment is so strong? Is that distinct? Do you envision any changes in the near future of surgery? I’m not talking about bulky disease.
Merrick I. Ross, MD: It’s really interesting because it’s somewhat of a data-free zone. You may say that’s very intensive therapy and it’s very effective, but whether it’s immune therapy or targeted therapy, it has been tested only in the context of patients having completion lymph node dissections for positive sentinel nodes. So we really don’t know how effective these therapies are in treating nodal disease. You can extrapolate from the data that if there’s a systemic response, the likelihood is that it’s also treating whatever disease is left behind in the microscopic level in patients who have not undergone a completion node dissection.
But I think it’s pretty clear that the completion node dissection added nothing in terms of survival to the adjuvant therapy trials. So that’s pure drug, certainly in my estimation. But we’re going to find out. We will find out how effective these therapies are, in terms of controlling nodal disease. We’ll certainly see patients who will have nodal disease as their first site of recurrence, and I’m hoping that’s their only site of disease when they have recurrence. Then they’ll be eligible for neoadjuvant trials. But that’s another question. How effective are these trials going to be after they’ve seen adjuvant therapy?
Axel Hauschild, MD: We will discuss it. Be patient, Merrick, we will discuss it.
Transcript Edited for Clarity