Progress in the application of combined detection of urinary tumor DNA and exosomes in the classification, staging, and clinical management of bladder cancer: a review

Bladder cancer (BC) remains a major clinical challenge due to its high recurrence rate and biological heterogeneity. Traditional diagnostic methods, such as cystoscopy and urine cytology, are limited by invasiveness and low sensitivity for early or low-grade tumors. Recent advances in liquid biopsy have highlighted the potential of urinary tumor DNA (utDNA) and exosomes as non-invasive biomarkers for diagnosis, molecular classification, staging, and therapeutic monitoring. utDNA reflects the genomic and epigenetic alterations of BC with high concordance to tumor tissue, while urinary exosomes serve as carriers of proteins, RNA, and DNA that mirror tumor biology and microenvironmental interactions. The combined detection of utDNA and exosomes significantly enhances diagnostic sensitivity and specificity, facilitates early disease detection, and enables a dynamic monitoring of treatment response and recurrence. Standardization of sample collection, analytical platforms, and data interpretation, together with multicenter clinical validation, is crucial for clinical translation. Future research integrating multi-omics profiling and artificial intelligence is expected to establish urinary liquid biopsy as a key tool for precision medicine in BC management.