Therapeutic options in metastatic uveal melanoma

Purpose Despite the advances in the treatment of uveal melanoma (UM), randomized studies have demonstrated that the metastatic risk was similar after enucleation or conservative treatment. Survival has not improved and enucleation remains the treatment of choice for large tumors. Methods Up to 50% of patients develop metastases, to the liver in 90% of cases,usually leading to death. Metastases are rarely detected at the time of diagnosis, and in contrast with cutaneous melanoma, occur via hematogenous spread. There is no standard adjuvant treatment to prevent metastases. Today, genome‐wide techniques of genomic and expression profiling make it possible to improve the characterization of high‐risk UM. Recently, mutations in the GNAQ/11 genes have been described as oncogenic drivers in UM and consequently potential therapeutic targets. Since the identification of genomic abnormalities correlated with the metastatic risk, techniques of fine needle aspiration biopsies have been developed and systematic genetic analysis of UM became recommended for the next years, in the prospect of future adjuvant trials based on potential biological targets to be tested in preclinical animal models. Results Relevant clinical data and dedicated studies in metastatic UM patients are lacking. Only 25 prospective clinical trials were published in the last 30 years,none of them reported a randomized phase III trial. In a retrospective series of 470 metastatic patients managed at Institut Curie (2000‐2008), the median overall survival was 13 months, with a significant difference according to the first treatment in the metastatic setting: 28, 12 and 4 months for liver surgery, any systemic treatment, best supportive care respectively Conclusion We will review current options and future developments for UM treatment.