The Diagnostic Accuracy of Methylation Markers in Urine for The Detection of Bladder Cancer: A Systematic Review

Abstract

Aim: Several urinary hypermethylation-markers (hmDNA) have been described for bladder cancer (BC) detection, but none have been able to replace cystoscopy yet. We systematically reviewed and evaluated current literature on urinary hmDNA markers for BC diagnostics. Patients & methods: A systematic search of PubMed, EMBASE.com and The Cochrane Library up to February 2017 using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, was conducted. Results: A total of 30/42 studies included compared gene panels, with varying sensitivities (52–100%) and specificities (0–100%). Considerable heterogeneity across studies was observed and most was case–control studies. Conclusion: Reported diagnostic accuracy of urinary hmDNA for BC detection is highly variable and there is a lack of validation studies. Recent studies indicate that complementary markers are needed to allow for clinical implementation.

Keywords::

• biomarkers
• methylation
• molecular diagnostics
• neoplasms
• urinary bladder
• urine analysis

Supplementary data

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https://www.tandfonline.com/doi/suppl/10.2217/epi-2017-0156

Financial & competing interests disclosure

RDM Steenbergen has a minority stake in Self-screen BV, a spin-off company of VU University Medical Center Amsterdam. EC Zwarthoff is an advisor for MDxHealth and is involved in research projects that were funded by MDxHealth. RDM Steenbergen, JA Nieuwenhuijzen, and LI Segerink. are named inventors on a patent application filed by Nanomed Diagnostics, which relates to the detection of hmDNA in urine. Application number: WO2017NL5019920170331. The authors have no other 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 apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

RDM Steenbergen has a minority stake in Self-screen BV, a spin-off company of VU University Medical Center Amsterdam. EC Zwarthoff is an advisor for MDxHealth and is involved in research projects that were funded by MDxHealth. RDM Steenbergen, JA Nieuwenhuijzen, and LI Segerink. are named inventors on a patent application filed by Nanomed Diagnostics, which relates to the detection of hmDNA in urine. Application number: WO2017NL5019920170331. The authors have no other 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 apart from those disclosed. No writing assistance was utilized in the production of this manuscript.