Sensitivity and prognostic significance of circulating tumor DNA (ctDNA) in stage I to III malignant melanoma

BACKGROUND: Risk stratification to guide adjuvant treatment in early stages of melanoma becomes increasingly important. This study investigated circulating tumor (ct)DNA in early melanoma stages to predict disease progression in real-world settings in German melanoma patients. METHODS: In this retrospective, single-center study, 61 patients with melanoma stages I-III with known disease-progression following primary diagnosis were included. Patients were requested to have baseline serum samples ≤ 4 weeks after diagnosis and ≥ 12 weeks preceding disease progression. In ctDNA isolated from 185 serum samples matching inclusion criteria, BRAF V600E/K, NRAS Q61K/L/R and TERT promoter mutations were quantified and correlated with serum levels of S100 and LDH. RESULTS: Mutated ctDNA was detected in ≥ 1sample in 43 of 53 patients (81.13%). CtDNA was more sensitive in the prediction of melanoma relapse than established biomarker S100, LDH (p < 0.001) and both LDH/S100 (p < 0.001). Highest mean ctDNA was measured during shift of stage III to stage IV disease (24.25 cps/µL) and shift within stage III (12.42 cps/µL). The detection of ctDNA at any time point trended towards shorter overall survival. CONCLUSION: Our study demonstrates the superiority of ctDNA harboring melanoma specific mutations over LDH and S100 in identifying patients at risk for recurrence in early melanoma stages in a single center cohort of melanoma patients. Future prospective trials are warranted to confirm this.