Diagnostic Performance of Biomarkers for Bladder Cancer Detection Suitable for Community and Primary Care Settings: A Systematic Review and Meta-Analysis

Evie Papavasiliou* (Corresponding Author), Valerie A. Sills, Natalia Calanzani, Hannah Harrison, Claudia Snudden, Erica D. Martino, Andy Cowan, Dawnya Behiyat, Rachel Boscott, Sapphire Tan, Jennifer Bovaird, Grant D. Stewart, Fiona M. Walter, Yin Zhou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Evidence on the use of biomarkers to detect bladder cancer in the general population is scarce. This study aimed to systematically review evidence on the diagnostic performance of biomarkers which might be suitable for use in community and primary care settings [PROSPERO Registration: CRD42021258754]. Database searches on MEDLINE and EMBASE from January 2000 to May 2022 resulted in 4914 unique citations, 44 of which met inclusion criteria. Included studies reported on 112 biomarkers and combinations. Heterogeneity of designs, populations and outcomes allowed for the meta-analysis of three biomarkers identified in at least five studies (NMP-22, UroVysion, uCyt+). These three biomarkers showed similar discriminative ability (adjusted AUC estimates ranging from 0.650 to 0.707), although for NMP-22 and UroVysion there was significant unexplained heterogeneity between included studies. Narrative synthesis revealed the potential of these biomarkers for use in the general population based on their reported clinical utility, including effects on clinicians, patients, and the healthcare system. Finally, we identified some promising novel biomarkers and biomarker combinations (N < 3 studies for each biomarker/combination) with negative predictive values of ≥ 90%. These biomarkers have potential for use as a triage tool in community and primary care settings for reducing unnecessary specialist referrals. Despite promising emerging evidence, further validation studies in the general population are required at different stages within the diagnostic pathway.
Original languageEnglish
Article number15030709
Number of pages35
Issue number3
Publication statusPublished - 24 Jan 2023

Bibliographical note

Funding: This research arises from the CanTest Collaborative, which is funded by Cancer Research UK [C8640/A23385]. YZ is funded by a Wellcome Trust Primary Care Clinician PhD Fellowship
(203921/Z/16/Z) and HH is supported by an International Alliance for Cancer Early Detection Project Award (ACEDFR3 0620I135PR007).

Data Availability Statement

The Search Strategy used in this systematic review has been provided
in Supplementary Materials. The datasets generated during the study are available from the corresponding author on reasonable request


  • bladder cancer
  • early detection
  • biomarkers
  • diagnostic performance
  • primary care
  • community


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