Nonsentinel Lymph Node Status in Melanoma Has Prognostic Value

Nonsentinel lymph node (NSLN) status in patients who underwent complete lymph node dissection after positive sentinel lymph node biopsy (SLNB) had independent prognostic value in patients with two to three positive lymph nodes, according to the results of a study published recently in the Journal of Clinical Oncology.

Furthermore, researchers led by Sandro Pasquali, MD, of the University of Padova, Italy, found that patients who had metastatic disease in their NSLN had their risk for melanoma death increased by more than one-third.

“It is still unclear whether the dismal prognosis of patients with NSLN metastasis merely reflects the prognostic value of a greater number of positive lymph nodes or is related to a different biologic behavior of lymph node metastasis beyond the SLN,” the researchers wrote. “Should the latter be the case, it is still unexplored how to include the NSLN status in the American Joint Committee on Cancer (AJCC) TNM staging system to improve patient risk stratification.”

The explore this issue further, the researchers collected retrospective clinicopathologic data from 1,538 patients who underwent complete lymph node dissection after positive SLNB and used a survival analysis to identify independent prognostic factors.

The researchers found NSLN metastasis in 23% of patients. After a median follow-up of 45 months, analyses showed that the presence of metastasis in NSLN was associated with a significantly worse prognosis (HR = 1.34; 95% CI, 1.18-1.52). In addition, metastasis was also linked with older age, male sex, and thicker primary tumors (P < .001 for all).

“To rule out the possibility that the independent significance of the NSLN status merely reflected the prognostic influence of a higher number of positive lymph nodes, the prognostic value of the NSLN status was tested separately in patients with the same number of positive LNs,” the researchers wrote.

Results indicated that patients with metastatic disease in one SLN and one NSLN had significantly worse prognosis compared with patients with two metastatic SLNs (P = .048).

Pasquali and colleagues then tested their hypothesis in patients with AJCC N2 and N3 status, indicating two to three, or four or more positive lymph nodes, respectively. Among patients with two to three positive lymph nodes, NSLN status effectively stratified prognosis (HR = 1.39; 95% CI, 1.07-1.81). However, NSLN status was no longer an independent prognostic factor among patients with four or more positive NSLNs.

Based on this finding, Pasquali and colleagues reclassified patients into four prognostic groups:

• Group 1: one positive SLN after SLNB and negative NSLN after complete dissection.

•Group 2: two to three positive SLN after SLNB and negative NSLN after complete dissection.

•Group 3: two to three positive lymph nodes including both SLN and NSLNs.

•Group 4: four or more positive lymph nodes including both SLN and NSLN.

This classification had prognostic significance (P < .001). Based on these classifications, patients in Group 3 (HR = 1.65; 95% CI, 1.23-2.23) and Group 4 (HR = 2.24; 95% CI, 1.59-3.20) had a significantly worse prognosis compared with patients in Group 1.

The researchers then combined this data with that of two other studies to conduct a meta-analysis summarizing available evidence on the prognostic value of NSLN status.

“The meta-analysis, which included 620 patients (284 had negative NSLN and 336 had positive NSLN), showed that the NSLN status is a highly significant prognostic factor for patients with two to three positive lymph nodes,” the researchers wrote.