A Simplified Classification System for In-Transit Melanoma Metastases

In-transit metastases (ITMs) are challenging to treat because of their heterogenous disease course and chronic, relapsing-remitting nature. Specific factors associated with worse prognosis are poorly understood and not included in current American Joint Committee on Cancer classifications. An ITMs-specific classification system to aid treatment decisions and clinical trial design is lacking.

This study involved 142 patients (M 44%, F 56%; median age 70 years [interquartile range 62-77]) with ITMs from a single, cutaneous melanoma. Baseline melanoma and ITMs characteristics, disease progression, and survival outcomes were collected from a prospective database. The primary outcome was disease-specific survival (DSS). A subgroup analysis excluding stage IV disease at diagnosis was performed.

A longer ITMs-free interval was associated with a longer DSS (hazard ratio [HR] 0.99; 95% confidence interval [CI] 0.98-1.00; p = 0.027). A higher number of ITMs and greater Breslow thickness was associated with a shorter DSS (HR 1.25; 95% CI 1.04-1.51; p = 0.020 and HR 1.10; 95% CI 1.04-1.17; p = 0.001). No independent predictors of DSS were identified. On multivariable analysis, larger ITMs and synchronous regional disease correlated with a worse distant metastasis-free survival (HR 1.02; 95% CI 1.03-1.31; p = 0.015 and HR 2.61; 95% CI 1.44-4.72; p = 0.002). Maximum threshold analysis selected the optimal cut-point for continuous variables: two lesions for number of ITMs and 30 mm for size at initial diagnosis, 2 mm for primary melanoma Breslow thickness, and 20 months for ITMs-free interval (time from primary melanoma diagnosis to ITMs onset), adjusted to 18 months for clinical relevance.

Patients presenting with more than two and/or >30 mm ITMs at first diagnosis, short ITM-free interval (≤18 months), and synchronous regional disease should be considered at higher risk for disease progression and death.