Liquid biopsy in genitourinary cancers: Diagnostic and prognostic implications

Table 1 Diagnostic parameters of liquid biopsy analytes in genitourinary malignancies as reported by meta-analyses

Cancer	Liquid biopsy	Sample size	Region	Cutoff	Sensitivity (%) (95%CI)	Specificity (%) (95%CI)	PLR (95%CI)	NLR (95%CI)4	Ref.
Bladder	CtDNA	748	Europe, Asia, United States	NA1	68 (54-78)	76 (51-90)	2.8 (1.24-6.35)	0.43 (0.28-0.65)	[17]
	UctDNA	1470	Europe, Asia	NA2	77 (61-88)	87 (77-93)	5.0 (3.2-10.7)	0.26 (0.15-0.47)	[23]
	CTC	2161	Europe, Asia, United States	NA2	34 (28-43)	97 (92-99)	11.8 (4.7-29.5)	0.68 (0.60-0.76)	[29]
	Plasma extracellular vesicles	5637	Asia, Africa	NA3	75 (73-78)	79 (76-82)	3.6(3.2-4.1)	0.31 (0.28-0.34)	[37]
	Urine extracellular vesicles	3348	Asia, Africa, United States	NA3	75 (71-78)	77 (74-80)	3.28 (2.9-3.7)	0.33 (0.29-0.37)	[39]
Prostate	CtDNA	3218	Europe, Asia, America	NA2	54 (47-61)	92 (88-95)	6.8 (4.9-9.5)	0.5 (0.43-0.58)	[54]
	CTC	No meta-analysis
	Plasma extracellular vesicles	1652	Asia, Europe, North America	NA1	70 (68-71)	79 (77-80)	3.33	0.38	[73]
Renal	CtDNA	1109	Europe, Asia, United States	NA1	71 (55-83)	79 (66-88)	3.42 (2.04-5.72)	0.36 (0.23-0.58)	[83]
	CTC	1088	Europe, Asia, United States	≥ 1 CTC	45 (31-60)	99 (97-100)	45	0.56	[88]
	Plasma extracellular vesicles	1680	Europe, Asia	NA2	86 (80-90)	80 (36-96)	4.3	0.7	[95]

¹No cutoff was reported in the study.

²Cutoffs differed among studies; some studies did not have cutoffs.

³No cutoff reported, only numerical concentrations.

⁴The 95% confidence intervals are reported when available. To note, all values and 95% confidence intervals are derived from the latest meta-analyses looking at these diagnostic markers. No meta-analysis looked at circulating tumor cells for diagnosis in prostate cancer. The positive likelihood ratio and negative likelihood ratio cells in grey were derived from sensitivity and specificity values; thus, no confidence interval is reported. The following formulas were used: Positive likelihood ratio = sensitivity/(1-specificity); Negative likelihood ratio = (1-sensitivity)/specificity. Most of the studies were conducted in Europe, Asia and North America, highlighting the need for further trials in the southern hemisphere. Additionally, the absence of a specific cutoff for the studies shows again a lack of standardization of the liquid biopsy protocols.

PLR: Positive likelihood ratio; NRL: Negative likelihood ratio; CI: Confidence interval; ctDNA: Circulating tumor DNA; uctDNA: Urine circulating tumor DNA; CTC: Circulating tumor cell; NA: Not available.