Prognostic Value of Non-nodal Regional Metastases in Predicting Sentinel Lymph Node Status in Cutaneous Melanoma: Multicenter Analysis of the Sentinel Lymph Node Working Group Database

BACKGROUND: Non-nodal regional metastases, including microsatellite lesions, satellites, and in-transit metastases, are an uncommon but aggressive entity in cutaneous melanoma. We evaluated their association with clinicopathological features, sentinel lymph node (SLN) status, and prognosis. PATIENTS AND METHODS: The Sentinel Lymph Node Working Group (SLNWG) database was used to examine the clinicopathological associations of non-nodal regional metastases, their prognostic significance in relation to SLN status, and their impact on clinical outcomes, including in patients with negative SLN status, using multivariable logistic regression and Cox regression models, respectively. RESULTS: Of 13,474 patients in the SLNWG database, 12,644 underwent SLN biopsy, and 3.4% (n = 426) had non-nodal regional metastases at diagnosis. These were associated with adverse clinicopathological features, higher odds of SLN positivity (OR 2.75; 95% CI 2.18-3.47; P < 0.001), and worse relapse-free survival (RFS: HR 1.47, 95% CI 1.07-2.02, P = 0.02), melanoma specific survival (MSS: HR 1.72, 95% CI 1.06-2.78, P = 0.03), overall survival (OS: HR 1.49, 95% CI 1.01-2.21, P = 0.05). Adverse prognostic associations were also observed in the SLN negative subgroup (RFS: HR 1.93; 95% CI 1.58-2.36, P < 0.001; MSS: HR 2.24; 95% CI 1.58-3.17, P < 0.001, and OS: HR 1.51; 95% CI 1.17-1.95, P = 0.002). CONCLUSIONS: Non-nodal regional metastases independently predict SLN involvement and adverse prognosis, and outcomes remain poor even when SLN is negative. These findings reinforce the risk stratification and prognostic relevance of SLN assessment in clinically node-negative patients with non-nodal regional metastases.