Value of quantitative and qualitative analyses of serum and urine cell-free DNA as diagnostic tools for bladder cancer: a meta-analysis

ABSTRACT

Background: Qualitative and quantitative analysis of circulating cell-free DNA (cfDNA) is a potential detection method for bladder cancer. Many studies have focused on the reliability of these results, but the conclusions have not been consistent.

Methods: We performed a diagnostic meta-analysis to investigate the diagnostic significance of serum and urine cfDNAs with tumor tissues as the standard control. We searched the MEDLINE, EMABASE, and Cochrane Central Controlled Trials Register (CCTR) databases until January 2019.

Results: A total of 11 studies involving early and/or advanced bladder cancer were finally included. The overall diagnostic accuracy was measured as follows: pooled sensitivity and specifcity were 0.69 (95%CI: 0.67, 0.71) and 0.72 (95%CI: 0.70, 0.74). Pooled positive likelihood ratio and negative likelihood ratio were 3.10 (95%CI: 2.35, 4.07) and 0.41 (95%CI: 0.34, 0.49). Combined diagnostic odds ratio was 8.26 (95%CI: 5.64, 12.11). A high diagnostic accuracy was demonstrated by the summary receiver operating characteristic curve, with area under the curve of 0.80 (95%CI: 0.77, 0.83).

Conclusions: CfDNA assay has high diagnostic value for the detection of bladder cancer. Larger sample studies are needed to further confirm our conclusions and to make this approach more sensitive and specific.

KEYWORDS:

• CfDNA
• diagnosis
• biomarkers
• meta-analysis

Article highlights

• Currently, the only non-invasive approach, urine cytology, has a low sensitivity for detecting low grade and early-stage tumors.

• Many studies have shown that cfDNA in serum/urine has potential value for bladder cancer screening, but the results across these studies were not consistent.

• The present diagnostic systematic review and meta-analysis demonstrated that the non-invasive cfDNA assay has high diagnostic value in bladder cancer patients.

• Using cfDNA in urine sediments to diagnose bladder cancer might has the best accuracy ability, still, due to the small patient number on urine sediments, future well large-scale studies are eagerly awaited to confirm the conclusion.

• In the future, larger sample studies are needed to further confirm our conclusions and to make this approach more sensitive as well as more specific.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Z Cao and L Peng and K He were involved in conception and design; drafting of the manuscript; and final approval of the manuscript. X Wang and Y Lu and Y Zhang were involved in acquisition of data; analysis and interpretation of data. Z Cao and L Bi were involved in critical supervision of the manuscript. All authors agree to be accountable for all aspects of the work.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This manuscript was supported by National natural science foundation of China (81572507) and Natural Science Foundation of Anhui Province (grant no. 1508085SQH225).