Is Complete Lymph Node Dissection Essential in Melanoma?

Sentinel lymph node biopsy in patients diagnosed with melanoma helps establish the spread of the disease beyond the cancer site. However, according to findings from a 63-center international study, complete lymph node excision may not be essential for improved melanoma outcomes.

Relatively rare, but significantly deadly, melanoma makes up less than 1% of skin cancers but is responsible for a majority of skin cancer deaths—almost 10,000 deaths are projected for 2017. Sentinel lymph nodes are routinely surgically removed because they are the closest draining lymph nodes where melanoma is known to spread. Standard treatment involves removing all nearby lymph nodes, which can sometimes trigger complications.

“They can have repeat hospitalizations for infections in their extremities. They can have life-limiting, painful swelling where they can't do the activities they like to do or wear their usual clothing. It's a significant, real problem for patients who are affected,” explained study author Tawnya L. Bowles, MD.

For the present study, called the Multicenter Selective Lymphadenectomy Trial II published in the New England Journal of Medicine, more than 3500 patients across 63 centers across the globe, including the Intermountain Medical Center and the Huntsman Cancer Institute in Salt Lake City, were recruited—1939 patients had an abnormal lymph-node biopsy. Patients were randomly assigned to standard-of care and had complete lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group)—ultrasounds were scheduled at every 4 months for the first 2 years, followed by every 6 months over the next 3 years. The primary trial endpoints included disease-free survival (DFS) and cumulative rate of nonsentinel-node metastases.

The study found that complete lymph-node dissection was not associated with increased melanoma-specific survival in patient data evaluated in an intent-to-treat analysis or 1755 in the per-protocol analysis, the authors write. The mean 3-year rate of melanoma-specific survival was similar between the dissection group (86±1.3%) and the observation group (86±1.2%; P = .42), as observed following a median follow-up of 43 months. DFS, however, was higher in the dissection group (68±1.7%) than in the observation group (63±1.7%; P = .05) at 3 years.

Important to note, however, is that nonsentinel-node metastases were a strong, independent predictor of recurrence in 11.5% of patients (hazard ratio, 1.78; P = .005).

“If the sentinel-node biopsy hadn't been done, the tumor present in the lymph node would have grown and progressed,” said Bowles. “Checking that lymph node is really important, but many patients can be spared taking out the others.”

She also pointed out the importance of immune therapy in these patients, especially in the context of distant metastases, which is the most common reason for mortality among patients with melanoma. The question is, would outcomes be different in patients treated with immunotherapies such as nivolumab or pembrolizumab in patients who do not have their lymph nodes removed?