Urinary Metabolomics Identifies Lactate as a Biomarker for Bladder Cancer Detection and Progression

Bladder cancer (BC) is the ninth most prevalent malignancy worldwide. It remains a significant clinical burden due to high recurrence rates and the need for reliable non-invasive diagnostic tools. Metabolomics is a powerful strategy for non-invasive cancer detection, with urine representing an ideal biofluid for biomarker discovery given its direct contact with the urinary tract and its rich diversity of metabolites. This study aimed to identify urinary metabolites showing significant differences in urinary levels between BC patients and controls, and to evaluate their potential for diagnosis and disease monitoring. Beyond identifying metabolites differentiating BC patients from controls, we also assessed whether urinary metabolic patterns could distinguish BC subtypes (non–muscle invasive vs. muscle-invasive, NMIBC vs. MIBC). Following chemical derivatization, urinary samples were analysed by gas chromatography–mass spectrometry (GC-MS), and the resulting datasets were evaluated using univariate and multivariate statistical approaches. Among the 32 metabolites identified (e.g., amino acids, organic acids, alcohols, sugar-derivatives), lactate was identified as significantly upregulated in BC versus controls, particularly in MIBC cases. ROC analysis demonstrated good performance for overall BC detection and in discriminating between MIBC and NMIBC cases. These results, independent of smoking status and sex, position lactate as a promising non-invasive biomarker for invasive BC.