Prognostic value of different biomarkers in bladder cancer: protocol for an umbrella review of systematic reviews and meta-analyses

Abstract

INTRODUCTION: Bladder cancer (BC), the second most common urinary cancer, is classified as either non-muscle-invasive BC or muscle-invasive BC. Although numerous studies have identified potential prognostic biomarkers, none have yet been implemented in clinical practice. A comprehensive umbrella review comparing all prognostic biomarkers in BC remains absent. Thus, we aim to synthesise evidence from systematic reviews and meta-analyses on prognostic factors in patients with BC. METHODS AND ANALYSIS: We will search PubMed/MEDLINE, Scopus, Web of Science (WOS), EMBASE, Cochrane Database of Systematic Reviews (CDSR), Google Scholar and EPISTEMONIKOS for systematic reviews of BC prognostic biomarkers from the inception date to 1 November 2025. Title and abstract will be screened for potentially relevant studies. Then two reviewers will independently select eligible reviews based on eligibility criteria. A data extraction sheet will be used to extract relevant information. The risk of bias in the included reviews will be assessed with the Risk of Bias in systematic reviews tool. Using the random-effects model for each prognostic biomarker, we will estimate the pooled HR and its 95 CI as well as the prediction interval and its 95 CI. To quantify heterogeneity between studies, we will use the I(2) metric. We will use contour funnel plots, doi plots, the Egger test and the Copas method to evaluate evidence of small-study effects. The credibility assessment will be assessed using the following items: level of statistical significance, number of cases, degree of statistical heterogeneity, significance of the PI, evidence of small-study effects and excess significance bias. We will perform sensitivity analyses with multiple approaches. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as primary data will not be collected in this study. The findings of this study will be disseminated through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42024602432.