Table 2.

Strengths and weaknesses of reviewed melanoma biomarkers.

Biomarker	Strengths	Weaknesses
CTC	• Sensitivity may be improved using multi-marker methods • Level fluctuations can be associated with treatment response, disease progression, and OS	• Short half-life in blood • Very low sensitivity in early-stage melanoma • Patients must have known melanoma markers • Levels not correlated with Breslow thickness
ctDNA	• Levels associated with tumor burden • Low or undetectable levels in metastatic melanoma patients associated with increased PFS and OS • May be used to determine first-line systemic therapy	• Short half-life in blood • Often not detectable in early-stage melanoma • Lack of consistent processes for collection, storage and detection • No established cut-off values • Patients must have known melanoma mutations
miRNA	• Highly stable • Multi-marker analysis may increase sensitivity	• Low concentration in blood • Lack of consistent processes for collection, storage and detection
EVs	• Moderately stable • May identify metastatic disease	• Low concentration in blood • Technical challenges with detection • Lack of consistent processes for detection and reporting