Uveal melanoma (UM) is a relatively rare cancer, but is the most common primary intraocular malignancy (see Chapter 25) and comprises 5% of all melanoma diagnoses in the United States.1,2 UM arises from melanocytes within the capillary-rich uveal tract, with the most frequent locations being the choroid (90%), ciliary body (6%), and iris (4%).3 Although UM occurs with an incidence of ~2,000 cases per year, it is an aggressive cancer.4,5 Screening with periodic, abdominal radiographic imaging, 25%–30% of patients are diagnosed with metastatic UM within 5 years (see Chapter 27). Exiting the eye by hematogenous spread, commonly reported metastatic sites include the liver (89%), lung (29%), and bone (17%).6 The latency between the treatment of the primary tumor and the emergence of metastases ranges from months to decades, underscoring the likelihood of early dissemination from the primary site and variable metastatic growth rates.7 Unfortunately, there is no standardized consensus and known effective treatment for advanced UM in the adjuvant or metastatic settings. The prognosis is poor once metastasis develops, with a median overall survival of 10.2 months.8 Long-term sur-vival is unusual except in rare patients with isolated liver metastases amenable to surgical resection. When available and clinically appropriate, treatment within a clinical trial is recommended.
Although UM differs from cutaneous melanoma both clinically and biologically, treatment options for advanced stages have largely been adopted with much lower resultant response rates.9 Similarly, in that UM metastases are less responsive than cutaneous melanoma to both chemotherapy and immune checkpoint inhibitors, several treatment modalities have been evaluated, including systemic chemotherapy, immunotherapy, and molecularly targeted agents for the MAPK pathway. As the most common initial site of metastasis is the liver, palliative management includes liver-directed therapies such as bland embolization, chemoembolization, radioembolization, immunoembolization, and hepatic arterial infusion of chemotherapy. In this chapter, we review the molecular pathogenesis of UM, its prognosis, and advances in the management of metastatic UM (Mind map 14-1).