Sentinel Lymph Node Biopsy Can Be Therapeutic in Melanoma Patients

Sentinel lymph node (SLN) biopsy without completion lymph node dissection (CLND) led to regional nodal disease control in melanoma patients, even those with risk factors for in-basin recurrence, according to an analysis of a randomized trial.

At 10-year follow-up, the SLN basin disease-free survival rate was 80.2% in patients randomized to nodal observation after removal of a positive SLN, reported Mark Faries, MD, of Cedars-Sinai Medical Center in Los Angeles, and colleagues.

Furthermore, no regional nodal basin recurrence was observed after 7 years, and patients with multiple risk factors, including older age, ulceration, Breslow thickness greater than 3.5 mm, non-axillary basin site, and tumor burden of maximum diameter of ≥1 mm and/or metastasis area of ≥5%, had basin disease-free rates ranging from 54% to 86% at 5 years, they noted in JAMA Surgery.

These results confirm “that definitive basin disease clearance is achieved in the great majority of patients with positive SLNs through the minimally invasive SLN-biopsy procedure itself,” Faries and team wrote. Thus, they suggested, while it has prognostic value, “SLN biopsy may also be regarded as therapeutic in some patients.”

They also noted that since the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) was conducted before the widespread availability of effective adjuvant systemic therapies, only 6.5% of observation patients received adjuvant treatment.

“Since early 2014, when patient accrual to MSLT-II was completed, multiple effective and relatively well-tolerated adjuvant systemic regimens have become widely available,” Faries and colleagues pointed out. “These therapies are expected to reduce the risk of nodal recurrence among observed basins even further than what we reported here.”

In a commentary accompanying the study, Douglas S. Tyler, MD, of the University of Texas Medical Branch in Galveston, and colleagues noted that “there is great value for patients never to experience SLN basin recurrence and to avoid the potential of needing a full nodal dissection with associated surgical morbidity. … Based on the current study, SLN biopsy is the only therapy ever needed to control the SLN basin in the vast majority of patients.”

Univariable analysis showed that freedom from regional nodal basin recurrence was associated with:

• Age younger than 50 years (HR 0.49, 95% CI 0.34-0.70)
• Non-ulcerated primary melanoma (HR 0.36, 95% CI 0.36-0.49)
• Less tumor thickness (less than 1.5 mm; HR 0.46, 95% CI 0.27-0.78)
• Axillary basin site (HR 0.61, 95% CI 0.44-0.86)
• Fewer positive SLNs (one vs three or more; HR 0.32, 95% CI 0.14-0.75)
• Lower SLN tumor burden (measured by diameter less than 1 mm: HR 0.39, 95% CI 0.26-0.60; measured by area less than 5%: HR 0.36, 95% CI 0.24-0.54)

On multivariable analysis, younger age (HR 0.57, 95% CI 0.39-0.84), less tumor thickness (HR 0.40, 95% CI 0.22-0.70), axillary basin site (HR 0.55, 95% CI 0.31-0.96), and smaller SLN metastasis diameter (HR 0.52, 95% CI 0.33-0.81; and HR 0.58, 95% CI 0.38-0.88) were independently associated with basin control.

“As clinicians consider alternative prognostic models through gene expression profiling of the primary melanoma, it is important to understand that the SLN excision provides excellent nodal control in addition to prognostic information,” Faries and colleagues concluded. “Age, primary tumor thickness, ulceration status, basin location, and SLN tumor burden were all independently associated with non-SLN status and, if validated, could be used to guide follow-up intensity and duration in the future.”

MSLT-II was an international phase III randomized trial that examined the utility of CLND versus nodal observation in melanoma patients with SLN metastases.

In an initial analysis, Faries and team found that immediate CLND was not associated with increased melanoma-specific survival. The current analysis was designed to determine how often SLN biopsy without CLND resulted in long-term regional nodal disease control in 823 patients randomized to observation.

Of these patients, 791 had one SLN-positive basin and 32 had two SLN-positive basins, for a total of 855 node-positive basins examined; 148 nodal recurrences occurred over the 10-year period, with most occurring by year 3.

Faries and colleagues noted that this analysis was limited as a single trial, and these findings should be confirmed in other data sets.