Table 1 Comparison of ctDNA and cfDNA Methylation Studies in Melanoma.

Lee et al.²⁹ (PMID: 29112704)

ddPCR

Plasma ctDNA

BRAF/NRAS

Not applicable

Not specified

Focused on monitoring relapse in Stage III melanoma: limited sensitivity for early detection. Evaluated pre-operative ctDNA detection in resected Stage l-lll melanoma. ctDNA was detected in 34% of patients overall. No data on Stage I. Sensitivity reflects Stage Ill-heavy cohort, not true early detection. Detection correlated with poor melanoma-specific survival

Tan et al.³⁰ (PMID: 30838379)

ddPCR

Plasma ctDNA

BRAF, NRAS, and other tumor-specific mutations

Not reported (Stage III only)

Not specified

Study enrolled 174 patients with resected Stage III melanoma. ctDNA was detectable in 37% of patients pre-operatively, and 49% post-operatively. ctDNA detection was associated with significantly increased risk of relapse and shorter relapse-free survival. This was a prognostic study, not early detection

Lee et al.³¹ (PMID: 30860590)

ddPCR

Plasma ctDNA

BRAF/NRAS/TP53

Not applicable

Not specified

Focused on high-risk Stage III cutaneous melanoma (N = 161). Pre-operative ctDNA detection in 28% of patients. ctDNA positivity was associated with significantly shorter recurrence-free and overall survival. Not a screening study; no early-stage (l-ll) patients were included

Klein et al.³² (PMID: 34176681)

Targeted methylation panel (> 100 k regions)

Plasma cfDNA

Methylation markers

0% (Stage I-III melanoma)

99.5% (all cancers)

Melanoma-specific sensitivity was 0% for stages l-lll and 100% for stage IV (N = 13 total). Highly specific but not optimized for melanoma detection

epiMelanoma (this study)

Targeted bisulfite NGS

Plasma cfDNA

Melanoma-specific methylation markers

26.7% (validation)

94.4% (validation)

epiMelanoma test shows moderate sensitivity in early stages and higher sensitivity in late-staqe disease