The Role of Lymphadenectomy in Node-Positive Melanoma
Panelists: Jeffrey S. Weber, MD, PhD, NYU Langone Health; Reinhard G. Dummer, MD, University Hospital of Zurich; Axel Hauschild, MD, PhD, University Hospital Schleswig-Holstein; Michael A. Postow, MD, Memorial Sloan Kettering Cancer Center; Caroline Robert, MD, PhD, Gustave-Roussy
Jeffrey S. Weber, MD, PhD: Interestingly, there’s both more work for the surgeons and less. The recent New England Journal article from Mark Faries, which was on the results of MSLT-II, has that impacted on practice in your hospital, Reinhard?
Reinhard G. Dummer, MD: Yes, absolutely, though the first conclusion for us was that with really microscopic disease, so below a tumor burden of 1 mm, these patients definitely don’t go for lymphadenectomy anymore. They get a closer follow-up with more ultrasounds. This has been changed. This has reduced the surgical approach by approximately 60% or 70%, because we had a lot of patients with very low tumor burden and the sentinel nodes. Actually, for the other patients with more involvement, we do a complete staging, because if you don’t do it you have no information about the stages of the other nodes. Unfortunately, a number of clinical trials really want to know that, so we do it for the sake of the clinical trials. This is obviously not the right way, so we have to be aware that we need data on patients who are not going to the full surgery program.
Jeffrey S. Weber, MD, PhD: If someone had more than a millimeter, would you advocate the completion lymphadenectomy?
Reinhard G. Dummer, MD: This is our strategy, because we want to know whether or not they would, for example, fit in an adjuvant clinical trial that was asking for the status. Obviously, the ongoing trials have to be adapted now, though a lymphadenectomy should not be mandatory for the inclusion in clinical trials.
Jeffrey S. Weber, MD, PhD: I think the new BMS adjuvant trials and CheckMate-915, which is now ipilimumab/nivolumab versus nivolumab alone, do not mandate a completion lymphadenectomy. So, it might be the first adjuvant trial to recognize and acknowledge the results of MSLT-II. Axel, in your hospital, do you routinely do a lymphadenectomy in anyone with a positive sentinel node or has the practice evolved?
Axel Hauschild, MD, PhD: I found your question very interesting, simply because the Germans changed the guideline 2 years ago. I just need to mention, Jeff, that there was another trial. It was exactly the same clinical trial design, done by Germans, but the number of patients was not convincing enough for very many United States physicians, including the surgical oncologists from the United States. So, when this was presented at ASCO and subsequently published in Lancet Oncology, Ulrike Leiter, who was the first, was criticized heavily because the trial was underpowered. But it found exactly the same result that MSLT-II confirmed now with more than triple the number of patients, with more than 1500 patients. We changed the guideline 2 years ago, so we are using exactly the Zürich scheme. With less than 1 mm, I think nobody is recommending a complete lymphadenectomy in sentinel node-positive patients. But for the more than 1 mm, we are saying in our guideline that it needs to be carefully discussed with the patient.
Now that the data are confirming the first German clinical trial, I think we need to have a very careful discussion. We shouldn’t forget in MSLT-II, there was a proportion of 18% of patients who had nonsentinel node positivity, which means lymph node metastases in nonsentinel nodes, which were only found with completion lymphadenectomy. Since we are doing the lymph node ultrasound approach, we hope that we can pick them up prior to the complete lymphadenectomy. We’re not sure.
Jeffrey S. Weber, MD, PhD: I assume the consensus is that the likelihood of a non-sentinel node being positive directly relates to the burden of tumor in the sentinel node. So, you can eliminate most of them by stratifying and picking and choosing.
Axel Hauschild, MD, PhD: By picking the right patients with high tumor load—those with extracapsular spread, very high tumor load. And honestly, I think there might be a subgroup of patients who still have a benefit. But once you have a strong adjuvant drug, you can discuss if this very small proportion of patients needs a complete lymphadenectomy with all the sequalae, which means lymphedema for the rest of their lives—particularly on the legs, if these were groin lymph nodes involved—and so on. And therefore, the data here at ESMO are convincing me that the role of the surgeon is a little weaker than ever before. I’m telling my patients, Jeff.
Jeffrey S. Weber, MD, PhD: In the stage 3 patients perhaps, but in the stage 4 patients…
Axel Hauschild, MD, PhD: No, no, I’m talking about stage 3 patients, because we’re talking about MSLT-II. This was just in stage 3 patients. I wanted to say that I’ve been telling my patients since a couple of years ago, “It’s not the surgeon curing you, it’s the biology of your disease killing you or curing you.” So, it’s not the surgical approach alone that is making the job. It’s the biology of the disease.