Treatment of Metastatic Uveal Melanoma in 2022

Improved Treatment Regimens and Improved Prognosis

David Reichstein; Anderson Brock; Caressa Lietman; Meredith McKean


Curr Opin Ophthalmol. 2022;33(6):585-590. 

In This Article

Abstract and Introduction


Purpose of Review: Until recently, metastatic uveal melanoma was associated with essentially uniform fatality within months. However, recent developments in screening, improved understanding of the genetic underpinnings of metastatic disease, and pivotal medication approvals have improved the disease's rate of fatality.

Recent Findings: Routine implementation of genetic testing at the time of primary tumor treatment via gene expression profiling or chromosomal analysis has identified patients who are at high risk for metastatic disease. Enhanced screening with imaging directed at the liver and lungs has allowed for identification of early disease and lower tumor burden. Significant work on improved liver directed therapy along with systemic chemotherapy and immunotherapy has improved life expectancy. The first systemic immunotherapy specifically for metastatic uveal melanoma was approved this year. This medication, tebentafusp, is likely to improve life expectancy for all patients with metastatic melanoma assuming they have appropriate human leukocyte antigen (HLA) markers. Multiple clinical trials with novel immunotherapeutic agents are promising as well.

Summary: The prognosis for patients with uveal melanoma is far better than ever before because of recent developments in the understanding and treatment of metastatic disease.


Uveal melanoma is the most common primary intraocular malignancy, and while several local therapies can be offered for primary disease control including plaque brachytherapy, proton therapy and enucleation, effective therapies to control distant disease have been limited.[1,2] Unfortunately, distant recurrence of uveal melanoma has traditionally been associated with mortality within 12–18 months.[3] Many patients with primary uveal melanoma experience metastasis – up to 50%, and multiple risk factors have been identified, including tumor size, cell type, local recurrence, or certain genomic characteristics.[4,5] The recent clinical implementation of genetic testing at the time of definitive primary tumor treatment, whether by gene expression profiling or by chromosomal analysis, has provided ophthalmic and medical oncologists with a validated prognostic tool at the time of diagnosis.[6] Further, the available genetic testing has been enhanced within the last decade. For example, gene expression analysis now includes routine testing for preferentially expressed antigen in melanoma (PRAME) and next generation cytogenetic testing.[7,8] This has further delineated the prognosis for patients once thought to have low-risk disease. We now know that a patient's initial prognosis as determined by tumor size and genetic makeup can guide frequency of screening with appropriate imaging of the chest and abdomen.

Early diagnosis of systemic recurrence allows for the opportunity for more therapeutic interventions to potentially alter the disease trajectory. Metastatic disease, once thought to be associated with imminent cancer-related death, is now a much more manageable issue assuming the patient is in the hands of an experienced medical oncologist in a center with significant melanoma expertise. The following review will highlight recent exciting progress in the treatment of metastatic uveal melanoma. These advances in the metastatic setting are also translating into clinical trials in the adjuvant space to prevent disease recurrence after completing local therapy.