Circulating Tumor Cells in Uveal Melanoma: Multi-Marker Detection and Association With Disease State

Purpose: Uveal melanoma (UM) is primarily treated with eye-sparing radiotherapy, leaving limited tumor tissue for molecular analysis. Circulating tumor cells (CTCs) may offer a minimally invasive alternative for genomic tumor profiling. This pilot study evaluated the feasibility of a multi-marker CTC capture approach in UM patients at diagnosis, during fractionated stereotactic radiotherapy (fSRT), and at metastatic progression. Methods: Patients with localized or metastatic UM were prospectively enrolled. Peripheral blood samples were collected at baseline, during fSRT, and on detection of metastases. CTCs were captured and enumerated using a multi-marker approach and fluorescence microscopy. Results: A total of 76 patients were included: 68 with localized disease and eight with metastatic disease. Four patients presented initially with localized disease but developed metastasis during follow-up: for comparisons, only metastatic-stage samples were used, yielding 64 localized and 12 metastatic samples. CTCs were detected in 69.1% of patients with localized disease at baseline and in 83.3% of those with metastases. CTC counts were significantly higher in metastatic disease than in localized disease (median = 8 vs. 3; P = 0.010). Among patients undergoing fSRT, paired analysis showed a significant increase in CTC counts between day 3 and day 5 (median = 1 vs. 4; P = 0.007). No significant associations were observed between baseline CTC counts and tumor thickness, largest basal diameter, tumor volume, American Joint Committee on Cancer tumor stage, tumor location, or molecular risk class. Conclusions: Multi-marker CTC detection in UM patients is feasible across disease stages. Increased CTC counts during fSRT may offer a window for molecular characterization. Larger studies with longitudinal blood sampling are needed to validate clinical and prognostic utility.