# A Simplified Classification System for In-Transit Melanoma Metastases

## TL;DR

This study proposes a new classification system for in-transit melanoma metastases to help guide treatment and clinical trials based on patient outcomes.

## Contribution

The paper introduces a simplified classification system for in-transit melanoma metastases based on specific prognostic factors.

## Key findings

- A longer ITMs-free interval was associated with better disease-specific survival.
- More ITMs and greater Breslow thickness were linked to worse survival outcomes.
- A classification system was proposed using cut-points for lesion number, size, and time intervals.

## Abstract

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.

The online version contains supplementary material available at 10.1245/s10434-025-18542-9.