Le Guin CHD, Bornfeld N, Bechrakis NE, et al. - A previous study demonstrated that detection of uveal melanoma (UM)-specific mutations and therefore cell-free tumor DNA (ctDNA) in the plasma of patients with metastatic UM is possible, researchers employed this assay to perform a prospective analysis in 135 consecutive UM patients for generating data on the temporal association between ctDNA identification in plasma and clinically detectable tumor progression. They used 807 blood samples to isolate cell-free DNA, which was analyzed for the presence of GNAQ/GNA11 mutations. Metastases or recurrence occurred in 21 of the 135 patients. In 17 of the 21 patients, plasma samples exhibited the presence of a ctDNA signal. This ctDNA signal, in 10 cases, was shown to precede the clinical diagnosis of metastasis by 2–10 months. In 10 other patients, only the samples collected shortly before or after radiotherapy demonstrated the presence of a ctDNA signal. In 16 of the remaining 125 patients, the existence of a ctDNA signal was shown to be associated with clinical manifestation of metastases (n = 14) or tumor recurrence (n = 2) with a sensitivity of 80% and a specificity of 96%. Findings indicate that identification of ctDNA in plasma can offer a diagnostic lead time over the clinical diagnosis of metastases or tumor recurrence. With shortened intervals between sampling, longer lead times are to be expected.