Uveal Melanoma: Biology, Prognostication, and Emerging Therapies to Outsmart an Immune-Cold Melanoma

Uveal melanoma (UM) is a rare but highly aggressive malignancy arising from melanocytes of the uveal tract. Despite high local control rates for primary disease, half of patients ultimately develop metastatic disease with historically dismal outcomes. Unlike cutaneous melanoma, UM is characterized by a low tumor mutational burden, distinct driver mutations, and an immunosuppressive tumor microenvironment which together limit the efficacy of immune checkpoint inhibitors. Over the past decade, major advancements in molecular classification, prognostication, and therapeutic development have reshaped the clinical landscape for some patients with UM. This review synthesizes the current understanding of UM epidemiology, characteristics, prognostic biomarkers, immune biology, and contemporary management for both localized and metastatic disease. While survival gains remain modest, the rapid expansion of biologically informed and immune-based strategies offers cautious optimism for improving outcomes in this historically treatment-refractory disease.