Management of liver metastases from uveal melanoma

Abstract

Uveal melanoma is the most common primary intraocular malignancy in adults, with distinct genetic and clinical characteristics compared with cutaneous melanoma. Despite improvements in the treatment of the primary tumour, nearly half of the patients will develop distant metastases, most commonly in the liver. Once metastases are detected, the median overall survival is approximately 1 year, with a 2-year survival rate of only 8%. Systemic treatment, including chemotherapy, immunotherapy, and targeted therapy, has historically shown limited efficacy. The first (and so far only) systemic treatment to demonstrate an improvement in overall survival is tebentafusp, which is now approved for treatment of patients with metastatic or unresectable uveal melanoma and an HLA-A*02:01 genotype. Liver-directed therapies include surgical resection, radioembolization, chemoembolization, immune-embolization, isolated hepatic perfusion, and percutaneous hepatic perfusion. This review discusses the clinical background of uveal melanoma and liver metastasis, the efficacy of systemic and locoregional treatment options, and the promising development of combining locoregional liver-directed treatment with systemic treatment.

Fig. 1

Genetic and cytogenetic determinants of metastatic risk in uveal melanoma GEP, gene expression profiling.

Fig. 2

Locoregional therapeutic options for uveal melanoma liver metastases a Example of locoregional treatment options for patients with uveal melanoma liver metastasis. b Isolated hepatic perfusion (IHP). c Percutaneous hepatic perfusion (PHP).

Fig. 2

Locoregional therapeutic options for uveal melanoma liver metastases a Example of locoregional treatment options for patients with uveal melanoma liver metastasis. b Isolated hepatic perfusion (IHP). c Percutaneous hepatic perfusion (PHP).

Fig. 3

Proposed treatment algorithm for patients with uveal melanoma metastases Besides the systemic treatments listed in the algorithm, eligible patients should be considered for inclusion in clinical trials investigating novel therapies. *Selection of locoregional treatment option is based on tumour size and anatomical location, and the treatment modalities available at the institution. CTLA-4, cytotoxic T-lymphocyte associated protein-4; PD-1, programmed cell death protein 1.