Table 1.

Advantages and disadvantages of standard tissue biopsy versus blood liquid biopsy versus urine liquid biopsy.

	Standard Tissue Biopsy	Blood Liquid Biopsy	Urine Liquid Biopsy
Components	Cell structure, grade, stromal and immune cells, Lymphovascular invasion, DNA seq, RNA seq, gene signatures	CTCs, cell free nucleic acids, exosomes, tumor educated platelets	Cell free DNA, urinary mRNA, miRNA, lnc RNA, other snc RNA, exosomes
Advantages	Standard of care Standard technique, low FNR Histological information and immunohistochemical profiling excellent	Minimally invasive procedure Early detection and molecular profile assessment Intratumor heterogeneity Real time monitoring of cancer evolution Corelates with tumor burden Identifies genetic markers of treatment and treatment resistance DNA fresh and not modified by storage technique Quick turnaround testing time for ctDNA ctDNA more beneficial in metastatic setting	Noninvasive procedure Early detection and molecular profile assessment Intratumor heterogeneity Large quantities available and centrifuged for concentrates High DNA yield Identifies genetic markers of treatment and treatment resistance Good for longitudinal follow up ucfDNA can potentially help in localizing “cancer of unknown primary”
Disadvantages	Invasive procedure, involves patient risk Lacks assessment of intratumor heterogeneity Time period of analysis fixed Repetitive invasive biopsies cumbersome Early detection of cancer not possible DNA quality highly variable in FFPE Variable quantity of DNA based on sampling methods, high risk of DNA degradation	Investigational setting High FNR Lack of standardized technique for cfDNA and cellular genomic DNA ctDNA quality and extraction methods. Short half life of CTCs (1–2.4 h) in peripheral blood	Investigational setting No histological assessment Effect of hydration status and medications ucfDNA integrity sensitivity and specificity issues Artifacts from microchip analysis Variations in assay protocols/sample handling Measurement of urinary RNAs challenging Lack of large multicenter studies

CTC: Circulating tumor cells; FNR: False negative rate; lnc RNA: Long non-coding RNA, sncRNA: small non-coding RNA; ucf DNA: urine cell-free DNA; RT-PCR: Reverse transcription polymerase chain reaction; FFPE: Formalin fixed paraffin embedded; ctDNA: circulating tumor DNA.