Table 5.

Summary of the studies evaluating the predictive role of circulating cell-free DNA (cfDNA) in renal cell carcinoma (RCC). AUC: area Under the Curve; gene: GA: genetic alteration; LOH: loss of heterozygosity; OS: overall survival; PCR: polymerase chain reaction; PFS: progression-free survival; qPCR: real-time polymerase chain reaction.

PREDICTIVE ROLE OF cfDNA IN RCC
Author, Year	Study Type	Purpose	Patients (n)	Controls	Sample Source, Amount	Timing Sample	cfDNA Isolation Method	Detection Method	Results
Feng, 2013, [61]	Prospective	Diagnostic Predictive	18 RCC (stage IV)	10 healthy individuals	Plasma, 0.4 mL	Six timepoints during treatment with Sorafenib: before treatment, 4–8–12–16–24 weeks	QIAamp DNA Blood Mini Kit (Qiagen)	qPCR	Pretreatment cfDNA levels were increased in RCC vs. healthy individual and were associated with stage, grade, and number of metastases. cfDNA levels from weeks 8 to 24 of treatment were higher in those with disease progression than in those with stable disease or partial response. Levels of cfDNA at 8 weeks were predictive of progression.
Rouvinov, 2017, [89]	Prospective	Predictive	23 RCC (stage IV)	-	Serum, 1 mL	Six timepoints during treatment with targeted therapy: before treatment, 4–8–12–16–24 weeks	QIAamp Blood Kit (Qiagene)	qPCR	Patients with normal pretreatment cfDNA level had a better PFS versus patients with increased levels. In multivariate analysis, cfDNA levels was associated with PFS.
Pal, 2017, [69]	Prospective	Predictive	220 RCC (stage IV)	-	Plasma, 1.5–2 mL	Pre-therapy Post-therapy	QIAamp Circulating Nucleic Acid Kit (Qiagen)	Targeted sequencing (73 genes)	GAs were detected in 78.6% of patients. The number of GAs was not correlated to line of therapy, but GAs in TP53 and NF1 increased with subsequent therapies.
Maia, 2017, [70]	Retrospective	Predictive	34 RCC (stage IV)	-	Plasma, 1.5–2 mL	Pre-therapy Post-therapy	QIAamp Circulating Nucleic Acid Kit (Qiagen)	Targeted sequencing (73 genes)	GAs were detected in 53% pf patients. cfDNA is a surrogate of tumor burner. No associations were found between ctDNA and IMDC risk, histology and response to treatment.