Identification of Predictive Factors for the Development of In-Transit Metastasis in Patients with Melanoma

Background: In patients with melanoma, in-transit metastasis (ITM) can develop. This study aimed to identify the risk for a first recurrence of ITM and associated predictive clinical factors in a large international cohort of patients with melanoma. Methods: Patients with primary cutaneous melanoma who underwent wide local excision (WLE) and sentinel lymph node biopsy (SLNB) were identified from the Sentinel Lymph Node Working Group (SLNWG) database between January 1993 and February 2023. Predictive factors for first recurrence of ITM were analyzed. Results: The study enrolled 7860 patients, and the median follow-up time was 47.1 months (interquartile range [IQR], 19.0–95.0 months). The risk for the development of ITM as a first recurrence was 4.12% (95% confidence interval [CI], 3.63–4.66%) at 5 years. The median time to first ITM recurrence was 15 months (IQR, 7.0–30.0 months). Significant clinicopathologic factors independently associated with an increased risk of ITM in multivariable analysis were increasing Breslow thickness (hazard ratio [HR], 1.37; 95% CI, 1.30–1.43; p < 0.0001), lower-extremity versus trunk melanoma (HR, 2.49; 95% CI, 1.86–3.32; p < 0.0001), increasing age (HR, 1.03; 95% CI, 1.02–1.04; p < 0.0001), number of positive sentinel lymph nodes (SLNs: 1 vs. 0 [HR, 2.24; 95% CI, 1.66–3.01; p < 0.0001] and 2 vs. 0 [HR, 2.37; 95% CI, 1.45–3.88; p = 0.0006]), and presence of vascular invasion (HR, 1.79; 95% CI, 1.21–2.64; p = 0.0035). Conclusion: The independent risk factors for the development of ITM identified in a large international cohort of melanoma patients were Breslow thickness, lower-extremity melanoma, older age, number of positive SLNs, and presence of vascular invasion.