Past
In-transit metastases are a challenging manifestation of cutaneous melanoma and are frequently encountered in modern practice.1 Unlike nodal or distant relapse, in-transit disease usually behaves as a chronic relapsing and evolving condition. Patients may experience a gradual increase in disease burden over time yet remain within the same AJCC stage.2 This disconnect between disease biology and staging creates uncertainty about prognosis and contributes to variation in clinical management. Decisions about whether to continue loco-regional control strategies or escalate to systemic therapy are often based on subjective interpretation and institutional bias, rather than objective criteria. Despite therapeutic advances, there remains no dedicated framework to stratify risk or inform treatment sequencing in patients with in-transit metastases.
Present
Our current study of 142 patients,3 treated within a quaternary-referral melanoma service, identified key clinical features that reflect aggressive in-transit disease behaviour. Patients with more than two lesions and/or those larger than 30 mm at initial presentation, or a short interval between treatment of the primary melanoma and development of in-transit disease (18 months or less) experienced significantly worse melanoma-specific survival. Synchronous nodal disease also correlated with poor distant metastasis-free survival. These findings suggest that not all in-transit disease is biologically equivalent, nor is the patient’s response to the disease and its subsequent treatment, and that early disease dynamics provide valuable prognostic information. By defining clinically relevant thresholds, our work offers a step towards classifying patients according to disease risk rather than anatomical pattern alone.
Future
We are hopeful that these results provide a foundation for the development of a simplified, clinically meaningful classification system for in-transit melanoma. Validation in external cohorts is now required, alongside further exploration of molecular and immune biomarkers to refine prognostic accuracy.4 Ultimately, a dedicated risk stratification framework could support personalised treatment strategies, consistency in reporting outcomes and rational stratification in future clinical trials.
Disclosure
This study received no funding from the public, private or not-for-profit sectors. The authors declare no conflicts of interest.
Footnotes
This article refers to: Breeze S, Peterson CM, Garioch JM et al. A simplified classification system for in-transit melanoma metastases. Ann Surg Oncol. 2025. (10.1245/s10434-025-18542-9).
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Sofia Breeze and Clare Peterson have listed alphabetically with equal academic merit.
References
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