Table4.

Advantages and limitations of CTCs vs. cfDNA

	Advantages	Limitations
CTC	Allows in depth assessment of viable metastatic tumor cells, DNA, RNA, and protein; may reflect mechanisms of resistance; may reflect treatment efficacy; allows functionally analysis (in vitro/in vivo testing)	Few and fragile; requires sophisticated isolation techniques; EMT may cause false negative results; tumor heterogeneity within CTCs; unclear which CTCs cause metastases
Cell free cfDNA	May reflect mechanisms of resistance; may reflect treatment efficacy; sensitive biomarker; available from other sources: urine, plasma, ascitic fluid	Present in inflammatory states and aging (not cancer specific); contamination with DNA from lysed cells; unclear if clinically relevant given being released from dying tumor cells; predetermined somatic alterations need to be identified; does not permit single cell analysis