Characteristics and Outcomes of Patients with Early or Late Uveal Melanoma Metastasis: A Review

Uveal melanoma (UM) metastasis follows variable temporal trajectories, with recurrences ranging from rapid onset to decades post primary therapy. Outcomes after metastasis also vary significantly. Predicting high-risk "early" progressors from "late" recurring phenotypes would facilitate tailored approaches to management.

A literature review was conducted to synthesise clinicopathologic and molecular predictors of metastatic latency and their impact on survival outcomes in patients with UM.

Early dissemination is associated with older age, male sex, larger basal dimensions, and ciliary body involvement. Genetically, monosomy 3, 8q gain, and BAP1 loss drives a rapid-progression phenotype and poor survival. Conversely, SF3B1 mutations define a distinct late-onset cohort (median: >6 years) with persistent lifetime risk. PRAME expression significantly accelerates metastatic kinetics, even in gene expression profiling class 1 tumours. While early recurrence correlates with dismal outcomes, late-onset disease is associated with extended post-metastasis survival and greater eligibility for interventions like liver-directed therapy.

Metastatic timing is related to biologic rather than stochastic determinants. Integrating molecular profiling with clinical staging and patient factors allows for more precise temporal risk stratification. These insights are essential for tailoring surveillance intensity and selecting candidates for emerging adjuvant therapies, such as tebentafusp and protein kinase C inhibitors.