Result of the phase III MLST-I clinical trial showed significantly higher 10-year disease-free survival rates for patients with intermediate-thickness or thick melanomas who had treatment based on results of a sentinel-node biopsy, compared with patients whose lymph nodes were monitored during clinical exams for signs of spreading disease. However, there was no significant treatment-related difference in 10-year melanoma-specific survival in the overall study population.

Final results from the phase III MLST-I clinical trial showed significantly higher 10-year disease-free survival rates for patients with intermediate-thickness or thick melanomas who underwent treatment based on results of a sentinel-node biopsy, compared with patients whose lymph nodes were monitored during clinical exams for signs of spreading disease. However, there was no significant treatment-related difference in 10-year melanoma-specific survival in the overall study population.

The node or nodes known as sentinels, identified through lymphatic mapping, are the first nodes that receive lymph from the tumor. Findings from the new study, published in February in The New England Journal of Medicine, show that the biopsy accurately identified the presence or absence of metastases in the sentinel node in 96% of cases.

The study's authors call the procedure, which predicts the tumor status of other nearby nodes, the “most powerful prognostic indicator” for melanoma patients. Patients in whom sentinel-node biopsy reveals metastases may undergo lymphadenectomy, surgery to remove lymph nodes. Having a sentinel-node biopsy, during which those nodes are examined for cancerous cells, has been widely adopted as part of the standard of care for melanoma patients who have a substantial risk of metastases to local lymph nodes, due in large part to early results from this study and others.

“The data show we now have a logical way to manage primary melanoma,” says Alistair J. Cochran, MD, from the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), who led the trial with the late Donald Morton, MD, from UCLA and the John Wayne Cancer Institute in Santa Monica, CA. “We have also demonstrated that if you have an intermediate-thickness melanoma, or a thick melanoma, the only way to determine whether it has spread to regional lymph nodes is to perform a sentinel-node biopsy.”

The researchers analyzed outcomes in 2,001 melanoma patients randomly assigned to undergo either sentinel-node biopsy or nodal observation following excision of the primary tumor. Patients in the biopsy group with intermediate-thickness (1.2 mm to 3.5 mm) melanomas had a 10-year disease-free survival rate of 71.3%, compared with 64.7% in the observation group. Patients in the biopsy group with thick (>3.5 mm) melanomas had a 10-year disease-free survival rate of 50.7%, compared with 40.5% in the observation group.

Cochran says researchers have been debating the best treatment for melanoma for more than a century. “You know that about one in five is going to get lymph node metastases, but they may not be clinically apparent at the time the diagnosis is made,” he says. If every patient went through lymphadenectomy, he notes, then 20% of patients will have been treated appropriately and 80% will have received unnecessary surgery. “So how do you treat the lymph nodes?”

That question, more than 20 years ago, led him and Morton to develop the lymphatic mapping procedure that identifies the sentinel node or nodes and to launch the clinical trial.

The follow-up phase III MLST-II trial is now testing whether melanoma patients with positive sentinel nodes benefit more from completion lymphadenectomy or observation using ultrasound.