Background
Phase III RCT (MSLT-I), N=2001 clinical stage I/II cutaneous melanoma. Primary analysis: intermediate-thickness melanoma (Breslow 1.2-3.5 mm). Stratified by tumor thickness. Enrolled 1994-2002 at 16 centers; final analysis 2014.
Interventions and follow up
Arm A: Wide local excision + sentinel-node biopsy (SLNB); immediate complete lymph-node dissection (CLND) if SLN positive
Arm B: Wide local excision + nodal observation; therapeutic CLND only on clinically detectable nodal recurrence
Primary endpoint: Melanoma-specific survival (MSS)
mFollow up: 10 years
Arm B: Wide local excision + nodal observation; therapeutic CLND only on clinically detectable nodal recurrence
Primary endpoint: Melanoma-specific survival (MSS)
mFollow up: 10 years
Results
10-yr MSS (ITT, intermediate-thickness): 86.0% vs 84.5%, HR 0.84, 95% CI 0.64-1.09, P=.18 (NS)
DFS (intermediate-thickness): HR 0.76, 95% CI 0.62-0.94, P=.01, favoring SLNB arm
10-yr MSS (SLN-positive vs observation node-recurrence): 62.1% vs 41.5%, HR 0.56, 95% CI 0.37-0.84, P=.006
SLN positivity rate: 20.8% of intermediate-thickness melanomas
DFS (intermediate-thickness): HR 0.76, 95% CI 0.62-0.94, P=.01, favoring SLNB arm
10-yr MSS (SLN-positive vs observation node-recurrence): 62.1% vs 41.5%, HR 0.56, 95% CI 0.37-0.84, P=.006
SLN positivity rate: 20.8% of intermediate-thickness melanomas
Adverse events
Lymphedema (immediate CLND vs observation): ~14% vs ~3%
Wound complications: higher in SLNB arm
Sensory neuropathy: reported in subset with CLND
Local excision alone: minimal morbidity
Wound complications: higher in SLNB arm
Sensory neuropathy: reported in subset with CLND
Local excision alone: minimal morbidity
Conclusions
SLNB improved DFS and provided accurate pathologic staging in intermediate-thickness melanoma but did not significantly improve MSS in the ITT population. Among SLN-positive patients, immediate CLND conferred superior MSS vs delayed CLND in a prespecified subgroup analysis.
Key Limitations
Primary MSS endpoint not met in ITT analysis. Key subgroup (positive SLN to immediate CLND vs observation-arm node recurrers) is a non-randomized comparison subject to lead-time and selection bias. ~20% of SLN-negative patients had regional recurrence, suggesting false-negative rate. Surgical technique variability across 16 centers over ~8-year accrual. Subsequent MSLT-II and DeCOG-SLT showed CLND after positive SLN does not improve MSS, undermining the subgroup conclusion.
Clinical Context
MSLT-I established SLNB as the standard staging procedure for intermediate- and high-thickness melanoma, identifying pathologically node-positive patients for staging and therapeutic decisions; ASCO/SSO guidelines endorse SLNB for these patients. MSLT-II (2017) and DeCOG-SLT (2016) later showed CLND after positive SLN does not improve MSS vs observation with surveillance ultrasound, so most patients now undergo active surveillance rather than immediate CLND.