The presence of cancer in the "sentinel" lymph nodes of melanoma patients should no longer be justification for automatically taking out all of the other unaffected lymph nodes, according to the authors of major clinical trial and an expert not involved in the study.
Instead, for patients with sentinel nodes (which are typically removed), the nodal basin should be observed over time for spread of disease – thus, immediate "completion dissection," which is a procedure with considerable morbidity, is avoided.
That is the upshot of the second Multicenter Selective Lymphadenectomy Trial (MSLT-II), the results of which were published online June 8 in the New England Journal of Medicine.
The study reports "high-level data that will change practice patterns internationally for melanoma patients," said study coauthor Jeffrey Farma, MD, a surgical oncologist at Fox Chase Cancer Center in Philadelphia, Pennsylvania, in an email to Medscape Medical News.
"These results should be construed as practice changing," agreed Daniel Coit, MD, a surgical oncologist at Memorial Sloan Kettering Cancer Center in New York City, in an accompanying editorial.
The new results are "definitive, unequivocal, and completely consistent" with other significant studies on this matter, including another randomized clinical trial, he wrote.
Regional lymph nodes are an "enigma," added Dr Coit. As a result, there has been a lack of understanding of exactly what role they play in disease, and a "more is better" approach to surgical removal has been adopted. He observed, however, that in melanoma, as in "so many other cancers," the elective removal of nodes that do not have clinical evidence of cancer "has rarely, if ever, been shown to increase disease-specific survival."
The procedure has been commonly practiced in melanoma patients, say the study authors. Because prospective evidence of the efficacy of the technique has been "lacking," the team undertook the current study.
At 63 international centers, the investigators randomly assigned patients with sentinel-node metastases (detected via standard pathologic assessment or a multimarker molecular assay) to either immediate completion lymph node dissection (n = 971) or to nodal observation with ultrasonography (n = 968).
In a per-protocol analysis, the mean 3-year rate of melanoma-specific survival, which was the primary endpoint, was similar in the dissection group and the observation group (86 ± 1.3% and 86 ± 1.2%, respectively; P = 0.42) at a median follow-up of 43 months.
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 = 0.05) at 3 years. This result was based on the increased 3-year rate of disease control (92 ± 1.0% vs 77 ± 1.5%; P < .001). But the authors do not give these findings much weight. "Since no significant difference between the groups was noted in the primary end point, differences with respect to the secondary end points must be interpreted with caution," they write.
Unsurprisingly, the patients who had more lymph nodes removed had a great risk of developing lymphedema. The condition was observed in 24.1% of the dissection group and in 6.3% of the observation group (P < .001). For most of the affected patients, lymphedema was mild (64%); for the remainder, lymphedema was moderate (33%) or severe (3%).
MSLT-II and another randomized controlled trial, DeCOG-SLT (Lancet Oncol. 2016;17:757-67), have "clearly shown that active surveillance of the nodal basin is a safe and efficient way to identify patients who are most likely to benefit from delayed, selective, node-directed treatment," summarized editorialist Dr Coit.
One Other Consideration
In this setting, however, one question remains, he also said. Namely, should any patient with sentinel node–positive melanoma undergo immediate completion lymph node dissection?
In other words, might there be some characteristics of the tumor (eg, Breslow thickness or ulceration) or sentinel node (eg, the number of positive nodes or the tumor burden) that would warrant earlier or immediate surgery in some patients?
The MSLT-II team reviewed the relevant data and found no associations between poorer outcomes and the various characteristics.
Dr Coit explains why: "This finding is almost certainly because the characteristics of patients who are at high risk for additional positive nonsentinel nodes are the same as those of patients who are at high risk for systemic metastases."
MSLT-II is a companion study to MSLT-I, which confirmed the staging value of sentinel node biopsy and showed that the technique slowed disease progression with early treatment of nodal metastases among patients with intermediate-thickness melanoma (N Engl J Med. 2014; 370:599-609).
However, the use of sentinel lymph node biopsy in MSLT-I "offers no survival advantage of any variety," said J. Meirion Thomas, FRCP, FRCS, a surgical oncologist at Imperial College, London, United Kingdom, in 2014.
"I repeat the charge that sentinel node biopsy in melanoma benefits doctors and hospitals but not patients, who may be considerably harmed by this intervention," he said at that time. "It is a staging procedure and nothing more."
The earlier trial was led by surgeon Donald Morton, MD, who is credited with developing the sentinel lymph node technique. Dr Morton died in 2014. That trial provided evidence for the use of sentinel node biopsy, which is now recommended in the guidelines of most national organizations, the study authors point out.
This is not the first randomized clinical trial to show that immediate completion dissection is necessary for patients with positive sentinel nodes. An American College of Surgeons Oncology Group trial, Z0011, found that completion lymph node dissection was not beneficial in a large subgroup of women with sentinel node positive breast cancer, as reported by Medscape Medical News. These data should further the understanding of regional node-positive disease, said Dr Coit.
The study was supported by grants from the National Cancer Institute and by funding from the Borstein Family Foundation, the Amyx Foundation, the Dr Miriam and Sheldon G. Adelson Medical Research Foundation, and the John Wayne Cancer Institute Auxiliary. Multiple study authors have ties to industry. Dr Farma has disclosed no relevant financial relationships.
N Engl J Med. Published online June 8, 2017. Abstract, Editorial
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Cite this: Practice-Changing Study for Melanoma Surgery - Medscape - Jun 12, 2017.
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