Prognostic and Predictive Value of ctDNA for Metastatic Uveal Melanoma: A Systematic Review and Meta-Analysis

Abstract

Metastatic uveal melanoma (mUM) is a rare disease associated with poor prognosis and limited therapeutic options. Recent studies showed that detecting ctDNA is feasible and can aid treatment decisions for patients with mUM. We systematically searched PubMed, EMBASE, and Cochrane databases for eligible studies published up to May 2025 that included patients with mUM and reported data on the association between ctDNA and survival outcomes (OS and PFS). Statistical analyses were performed using Review Manager 5.4 software. Of the initial 450 records, seven studies met eligibility, including 518 patients with mUM. At baseline, ctDNA positivity was associated with significantly worse PFS (HR 2.34; 95% CI 1.56–3.51; p < 0.01; I² = 0%) and OS (HR 3.32; 95% CI 2.09–5.29; p < 0.01; I² = 48%). In patients treated with tebentafusp, ctDNA clearance was associated with superior OS (HR 0.19; 95% CI 0.07–0.49; p < 0.01; I² = 46%) and any decrease in ctDNA was associated with better OS (HR 0.42; 95% CI 0.22–0.80; p < 0.01; I² = 0%). This meta-analysis underscores ctDNA as a potential predictor of worse survival in patients with mUM, highlighting its potential to refine risk stratification and guide treatment strategies.

Trial Registration: International Prospective Register of Systematic Reviews (PROSPERO): CRD42025638076