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

SIMPLE SUMMARY: Bladder cancer (BC) is one of the most common cancers worldwide. Early-stage diagnosis is associated with better survival rates and, as such, the timely referral of suspected cases is paramount. Urinary biomarkers have been developed to aid diagnosis, and are largely tested in patients who have been referred for further investigation. Evidence, however, on their diagnostic performance for both detecting and ruling out BC, especially in the general population, is limited. In this review, we systematically identified studies reporting on the diagnostic performance of biomarkers suitable for use in primary and community care settings. Three biomarkers, with relatively little difference in diagnostic performance between them, and some novel biomarkers were identified showing potential to be used as a triage tool in such settings. While promising, further validation studies in the general population are needed. ABSTRACT: 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.