Management of metastatic uveal melanoma: French expert consensus guidelines

Uveal melanoma (UM) is a rare malignancy originating from uveal melanocytes. Despite effective control of the primary tumour, metastatic uveal melanoma (MUM) occurs in approximately 20-30% of patients, primarily affecting the liver, with a poor prognosis and overall survival (OS). The unique molecular profile of UM, lacking BRAF, NRAS, and KIT mutations, limits targeted therapy efficacy. Chemotherapy and immune checkpoint inhibitors (ICIs) also show limited benefits, while tebentafusp has emerged as the first drug to improve OS, but this systemic treatment can be used only in HLA-A*02:01-positive patients. A French multidisciplinary panel developed evidence-based guidelines for MUM management presented in this review. Recommendations emphasise on comprehensive diagnosis, including liver biopsy and imaging, circulating tumour DNA (ctDNA) analysis, and high-definition HLA typing for HLA-A*02:01. Local therapies are proposed for patients with limited hepatic metastases, from liver surgery to isolated hepatic perfusion and chemoembolisation for patients with more extensive hepatic involvement. Systemic therapy with tebentafusp is the standard of care for HLA-A*02:01-positive patients. For HLA-A*02:01-negative patients with extensive disease, treatment options are limited. They are encouraged to participate in a clinical trial, alternatively, percutaneous hepatic perfusion, ICI alone or in combination can be proposed. Treatment efficacy assessment includes response evaluation criteria in solid tumours (RECIST), tumour growth rate (TGR) analysis, and ctDNA dynamics. This consensus provides practical guidelines for French oncologists to optimise MUM management, integrating locoregional interventions, systemic therapies, and biomarkers to enhance patient outcomes.