A recent trial found no survival difference in patients with melanoma with a positive sentinel lymph node biopsy who underwent complete lymph node dissection compared with those who did not undergo dissection. However, the trial failed to achieve the required number of events and is, therefore, underpowered.
No difference in survival was identified in patients with melanoma with a positive sentinel lymph node biopsy who underwent complete lymph node dissection compared with those who did not undergo dissection, according to the results of the phase III DeCOG-SLT trial published in Lancet Oncology. However, the trial failed to achieve the required number of events and is, therefore, underpowered.
According to Ulrike Leiter, MD, of Eberhard-Karls-University of Tuebingen, Tuebingen, Germany, and colleagues, they expected 192 distant metastatic events to occur after 3 years. The study had only 85 events, leading to a decrease in the power of statistical testing from 80% to 50%. Despite this, Leiter and colleagues concluded that “on the basis of our findings, complete lymph node dissection should not be recommended in patients with melanoma with micrometastases, at least those with single cells or micrometastases 1 mm in size or smaller.”
The multicenter study enrolled patients with melanoma of the torso, arms, or legs between January 2006 and December 2014. Patients underwent sentinel lymph node biopsy, and those who consented were randomly assigned to undergo complete lymph node dissection or observation with permuted blocks of variable size. The primary endpoint was distant metastasis-free survival.
“Patients with sentinel lymph node biopsy of the head and neck were not included in the study, as sentinel lymph node biopsy in the head and neck region was controversial and was not done in every melanoma center when the study was planned in 2002–2004,” the researchers noted.
The study screened 5,547 patients and 1,269 patients (23%) were positive for micrometastasis after sentinel lymph node biopsy. Of those with a positive biopsy, 39% agreed to randomization. About two-thirds of patients had a metastases of 1 mm or smaller.
After a median follow-up of 35 months, distant metastases occurred in 18% of patients. In the intention-to-treat analysis, the 3-year distant-free survival was 77% in the observation group compared with 74.9% in the dissection group (hazard ratio [HR], 1.03 [95% CI, 0.71–1.50]). Three-year overall survival was 81.7% for patients who were assigned to observation compared with 81.2% for those who underwent dissection (HR, 0.96 [95% CI, 0.67–1.08]). In addition, recurrence-free survival was also similar between the two groups.
About one-fourth of patients assigned to dissection experienced an adverse event. Overall, grade 3 events occurred in 6% of patients assigned to dissection, and grade 4 events occurred in 8%; these events included lymphedema, lymph fistula, seroma, infection, and delayed wound healing.
“Despite limitations of the DeCOG trial, our results could have important implications for clinical practice,” the researchers wrote. “The only rationale for complete lymph node dissection in sentinel lymph node biopsy–positive patients would be if the finding of additional nodal metastases would result in changes in adjuvant systemic therapy. As there are no differences in adjuvant systemic therapy based on the number of positive lymph nodes, complete lymph node dissection appears to be dispensable.”
In a comment published with the study, Charlotte Ariyan, of Memorial Sloan Kettering Cancer Center in New York, stated that despite the trial being underpowered, it is unlikely that further accrual would have changed outcome given that there was “no difference in all variables examined, and almost completely overlapping curves” for distant metastasis-free survival, recurrence-free survival, and overall survival.
“In the DeCOG trial, 36 (15%) of 242 patients randomly assigned to complete lymph node dissection withdrew their consent in order to undergo observation, whereas only 1% of patients randomly assigned to observation withdrew their consent,” she wrote. “On the basis of the results of this prospective randomized trial, the National Comprehensive Cancer Network changed the guideline after a positive sentinel lymph node biopsy from complete lymph node dissection to discuss and offer complete lymph node dissection.”