Complete Lymph Node Dissection Not Superior to Surveillance in Melanoma

Daniel Coit, MD

For patients with melanoma who have positive sentinel lymph nodes (SLNs), practitioners now have phase III evidence that suggests that complete lymph node dissection (CLND) is not more effective than observation and nodal ultrasonography.

The international, multicenter, randomized MSLT-II trial evaluated the efficacy of CLND in melanoma patients with SLN metastases (n = 824) compared with that of observation and nodal ultrasonography (n = 931). In the per-protocol analysis and at median follow-up of 43 months, the mean 3-year rate of melanoma-specific survival (MSS) was similar in the dissection group (86 ± 1.3%) and the observation group (86 ± 1.2%), respectively (P = .42). The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68 ± 1.7% and 63 ± 1.7%, respectively; P =.05) at 3 years.

“The data upon which the recommendation is made to no longer pursue this immediate lymph node dissection—the data are absolutely unequivocal,” said Daniel Coit, MD. “There is no reason I can think of that a patient would have a CLND.”

OncLive: What is the current state of SLNs and CLND in melanoma?

What is the background of these impactful clinical trials?

What other trials are being looked at in this area with melanoma? Or, do we have all of the questions answered?

With several novel agents now in the melanoma armamentarium, what does the role of surgery look like to you in the future?

Coit, a surgical oncologist at Memorial Sloan Kettering Cancer, and professor of surgery at Weill Cornell Medical College, shared insight on the clinical findings regarding CLND and the evolution of surgery in the melanoma landscape in an interview during the 2017 OncLive^® State of the Science Summit^TM on Melanoma.Coit: Habitually, in a patient with melanoma who has a positive SLN, we have felt it important to remove the rest of the lymph nodes. There are now 2 large prospective clinical trials that have unequivocally shown that removal of more lymph nodes at the time of a SLN biopsy confers absolutely no advantage in terms of MSS. For the most part, the consistency of these data and the size of these trials would suggest that when a SLN is found to be positive in a patient with melanoma, that is not the time to perform a CLND. There were 2 trials. One trial is from Germany, and a subsequently much larger trial is from multiple centers around the world, which took patients with melanoma and positive SLNs and randomly allocated them to closed ultrasound nodal basin surveillance or immediate CLND. In follow-up, there was no difference in either distant metastasis-free survival or overall survival. These 2 trials were really practice-changing, and they answered the questions definitively and unequivocally. There are other series looking at this, but none of these series, either retrospective or prospective, will be anywhere near as definitive as these 2 trials have been. The role of surgery is evolving in melanoma; there’s no question about it. Surgery will always be a part of the critical part of the upfront management or the initial diagnosis of patients. Surgery is becoming de-emphasized a bit entirely in patients with positive SLNs. In the patients with clinically positive nodes, the role of surgery is going to evolve. If you ask me to predict the future, it will evolve as we integrate neoadjuvant strategies, hopefully to the benefit of the patient, minimizing the extent of surgery and morbidity.

What challenges are we currently facing in melanoma regarding surgery?

Let’s say you get a patient with melanoma in your office. What factors do you consider in deciding whether they will receive neoadjuvant treatment or go straight to surgery?

What are the key takeaways that you hope community oncologists receive from this lecture?

The most interesting area evolving of surgery in melanoma is clearly in patients with advanced or metastatic disease. We're having more and more scenarios and opportunities for surgery to intervene in the management of these patients. In fact, there were 2 articles in the New England Journal of Medicine recently that looked at what happened after patients recurred on clinical trials. One was on adjuvant therapy, and one was focused on treatment for advanced disease. In both series, about 20% of the patents who relapsed on those trials had surgery required as part of their management. That is a growing area in melanoma. There is almost a draw in surgery toward technology. One of the draws is toward the application of minimally invasive techniques in surgery. There are certain scenarios where minimally invasive techniques have a lot to offer patients with melanoma, particularly those with limited pelvic lymph node involvement. Here, the open operation can be quite morbid and require quite a bit of recovery. Minimally invasive operations can get patients out in a day or so and accomplish the same thing. Therefore, there will be some evolving technology there. Clearly, there have been some other areas where technology has been leveraged in areas of radiation therapy, where we can apply much more focused areas in need while sparing normal tissues. We have not really defined the indications for neoadjuvant therapy—who should and should not get it. Right now, a lot of that is being done either on a case-by-case basis, or preferably in the context of a clinical trial, to try to define the indication for who should and should not get neoadjuvant therapy. We don’t know if it’s better than postoperative adjuvant therapy; that is an area of investigation. We don’t know the answers to that.The main takeaway of the talk is that the immediate decision about CLND in a patient with melanoma with a positive SLN is not something we should focus on. We need to focus on nodal observation and delayed lymph node dissection if the patients recur in the nodal basin alone. That is an increasingly important change in how we've treated patients. It is going to take a while to get that message out, and tonight was another opportunity to try and do it.

Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376:2211-2222. doi:10.1056/NEJMoa1613210.