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Objective To evaluate the efficacy of different therapeutic modalities in the treatment of metastatic uveal melanoma (mUM). Methods According to PRISMA criteria, We identified relevant randomized controlled trials (RCTs) by searching PubMed, Embase, and The Cochrane Library through March 31, 2026. Patients with liver metastatic uveal melanoma were enrolled. The analysis of clinical prognostic factors was performed using R 4.2.0. The main outcomes measured were overall survival (OS) and progression-free survival (PFS). Results A total of 16 articles were screened between 2000 and 2026, involving 2585 patients. The trials evaluated eight treatment approaches: tebentafusp, immune checkpoint inhibitors (ICIs), targeted therapy, targeted therapy plus chemotherapy, chemotherapy, liver-directed therapy (LDT), liver-directed therapy combined with ICIs, and liver-directed therapy plus chemotherapy. The results of the included trials showed that in terms of overall survival and progression-free survival, the liver-directed therapy combined with ICIs were the most effective regardless of the HLA genotype. Tebentafusp showed the second-best OS but the worst PFS among the compared treatments. Immune checkpoint inhibitors were inferior to tebentafusp in improving OS but were superior in PFS. Furthermore, compared with conventional systemic chemotherapy, targeted therapy, or their combination, regional liver-directed therapy demonstrated more favorable outcomes in both OS and PFS. Emerging immunotherapies (e.g., tumor vaccines, oncolytic virotherapy, tumor-infiltrating lymphocytes) and novel targeted agents could not be included in the NMA due to the absence of comparative trials or ongoing investigations. Conclusion The liver-directed therapy combined with ICIs achieved the best results compared to Tebentafusp, ICIs and other therapeutic modality for OS and PFS extension in metastatic uveal melanoma based on available data. Future comparative studies incorporating emerging therapies are warranted. Systematic Review Registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261393862.
Chen et al. (Wed,) studied this question.