Non-Invasive Urine-Based Diagnostic Technologies for Early Bladder Cancer.

Bladder cancer (BCa) is a major global urinary tract malignancy characterized by high incidence, frequent recurrence, and significant mortality. Early diagnosis is crucial for improving prognosis and minimizing invasive procedures; however, current standard techniques, cystoscopy and urine cytology, are limited by invasiveness, cost, low sensitivity, and subjectivity. This has spurred the development of non-invasive diagnostic strategies based on urine analysis. This review highlights five emerging approaches: AI-augmented urine cytology, genomic biomarker assays (e.g., PCR and NGS for mutations and copy-number variations), DNA methylation profiling, RNA biomarkers (mRNA, miRNA, lncRNA), and protein/peptide/metabolite detection utilizing ELISA, SERS, nanozymes, and mass spectrometry. We assess the diagnostic accuracy, innovations, and clinical potential of each, while addressing persisting issues such as lack of standardization, high costs, and insufficient sensitivity for early-stage lesions. Future directions include integrating multi-omics data with AI, advancing point-of-care devices, and conducting large-scale multicenter trials. Together, these developments promise to shift BCa management toward molecular-based early detection, enabling more precise, non-invasive, and personalized patient care.