SLN Biopsy Promising for Long-term Metastatic Melanoma Control

Known to be effective for staging cutaneous melanoma, sentinel lymph node (SLN) biopsy was investigated in the second Multicenter Selective Lymphadenectomy (MSLT-II) for potential effectiveness against SLN metastases and shown to provide long-term regional nodal disease control.

Outcomes from a subanalysis of MSLT-II data were investigated among 823 patients (58.2%, male patients; mean [SD] age, 52.8 [13.8] years) randomized to completion lymph node dissection (CLND) or nodal observation, and the findings from the prospective multicenter randomized phase 3 clinical trial were recently published in JAMA Surgery. Frequency of long-term disease control following SLN biopsy that did not require CLND was the primary objective, with the main outcome being in-basin nodal recurrence. The data collection window was December 2004 to April 2019 and the analyzation period, July 2020 to January 2022. To be included in the final analysis, patients had to have an Eastern Cooperative Oncology Group performance status of 0 to 1 and non–melanoma-related life expectancy of ate least 10 years.

“The absence of a significant overall survival benefit from CLND has led to the suggestion that SLN biopsy is merely a staging procedure, without therapeutic value,” the authors wrote. “Certainly, the question of whether there is any overall survival effect of early nodal surgery remains controversial, but there is little published information regarding the effect of SLN biopsy alone (ie, without CLND).”

There were 855 observed basins—791 patients had 1 each and 32 patients had 2 each—among which there was an 80.2% (95% CI, 77%-83%) nodal recurrence–free rate. Univariable and multivariable analyses were performed, and both showed reduced risks of regional nodal recurrence.

Univariable analysis following SLN biopsy showed the following:

• 51% reduced risk in persons younger than 50 years (HR, 0.49; 95% CI, 0.34-0.70; P < .001)
• 64% reduced risk if the melanoma was nonulcerated (HR, 0.36; 95% CI, 0.36-0.49; P < .001)
• 54% reduced risk from primary melanomas that were thinner than 1.5 mm (HR, 0.46; 95% CI, 0.27-0.78; P = .004)
• 39% reduced risk in the presence of an axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005)
• 68% reduced risk if there was 1 vs 3 positive lymph nodes (HR, 0.32; 95% CI, 0.14-0.75; P= .008)
• 61% and 64% reduced risks, respectively, in the presence of a smaller SLN tumor burden:
  • Diameter < 1 mm (HR, 0.39; 95% CI, 0.26-0.60; P= .001)
  • Area < 5% (HR, 0.36; 95% CI, 0.24-0.54; P < .001)

Multivariable analysis for basin control echoed the above positive findings:

• 43% reduced risk from with younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004)
• 60% reduced risk from thinner melanomas (HR, 0.40; 95% CI, 0.22-0.70; P = .002)
• 45% reduced risk in the presence of an axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03)
• 48% reduced risk if SLN metastasis diameter is less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007)
• 42% reduced risk if SLN metastasis area is below 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01)

An additional analysis showed decreasing basin disease-free rates with increasing total risk factors. When considering age 50 years or older, ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumors that were 1 mm or more thicker or tumors that had a metastasis area greater than 5%, the 5-year disease-free rate dropped from 96% if a patient had none of these risk factors to 80% with 3 risk factors to 54% with 5 or 6 risk factors present.

The study authors note that MSLT-II findings, as well as those from the German Cooperative Oncology Group Selective Lymphadenectomy Trial, changed SLN metastasis treatment guidelines “to allow for nodal observation, which has become standard practice for patients with SLN metastases.”

As a result, however, the approach has led to gaps in knowledge of the disease and further studies are needed to validate their findings.

“Our study helps continue the process of adapting clinical care to nodal observation after SLN metastasis and raises new questions for management,” the authors concluded.

Reference

Multicenter Selective Lymphadenectomy Trials Study Group. Therapeutic value of sentinel lymph node biopsy in patients with melanoma: a randomized clinical trial. JAMA Surg. Published online August 3, 2022. doi:10.1001/jamasurg.2022.2055