Metabolomic Biomarkers for Prognosis in Non-Muscle Invasive Bladder Cancer: A Comprehensive Systematic Review and Meta-Analysis

The prognostic biomarkers, or metabolites, have gained relevance due to their significance in predicting clinical and therapeutic outcomes and guiding informed therapy options. This systematic review and meta-analysis aimed to evaluate the prognostic significance of metabolites in non-muscle-invasive bladder cancer (NMIBC) through an array of literature. The PubMed, Web of Science, Embase, and Cochrane Library databases were comprehensively searched for eligible studies published between January 2010 and August 2022, using related keywords and MeSH terms. Two reviewers performed the extraction process, and a third reviewer settled possible controversies. The New Castle Ottawa scale (NOS) was used to determine the quality of selected studies. Pooled hazard ratios (H.R.s) with 95% confidence intervals (C.I.s) were calculated to establish the relationship of metabolites with NMIBC outcomes (recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (O.S.) to establish their prognostic roles. A total of 15 studies, with a sample size of 5491, were included and analyzed in this study. Various metabolites were found to be correlated with the outcomes of the study: PFS (pooled HR, 4.48; 95% CI, 1.70–11.80, p = 0.002), RFS (pooled HR, 2.85; 95% CI, 1.91–4.26; p = 0.00001), and OS (HR, 1.78; 95% CI, 1.07–2.98; p = 0.03). Pretreatment metabolites or markers in NMIBC patients had a relationship with recurrence prediction and disease outcomes in bladder cancer. Therefore, metabolites may equally serve as a critical, independent prognostic predictor for NMIBC patients. This could be considered in most related clinical decisions in bladder cancer.