Multidimensional liquid biopsy in bladder cancer: advances in circulating tumor cells, circulating tumor DNA, exosomes, and metabolomics

Bladder cancer (BCa), marked by clinical heterogeneity and late diagnosis, remains a global health challenge. The limitations of conventional diagnostics have spurred the advancement of liquid biopsy approaches, which offer minimally invasive tools for early detection, prognosis, and therapeutic monitoring. This review highlights key components of liquid biopsy in BCa, including circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, and metabolomics-especially urinary volatile organic compounds (VOCs). Each modality contributes distinct insights into tumor biology: CTCs and ctDNA provide information on tumor genetics and dynamics; exosomes reflect microenvironmental signaling and lipid metabolism; and urinary VOC profiling enables metabolic characterization and early-stage discrimination. We explore how these dimensions complement each other in tracking disease progression, predicting recurrence, and guiding personalized therapy. Emphasis is placed on recent technological advances, clinical utility, and future integration into practice. This multidimensional perspective underscores the transformative potential of liquid biopsy in improving BCa outcomes.