Molecular testing in urinary cytology specimens: Current status and future directions.

Bladder cancer is a common type of urological cancer with high recurrence and mortality rates. Currently, it is diagnosed and monitored using minimal invasive cystoscopies and biopsies. Urinary cytology, the most widely accepted noninvasive and more economic urinary diagnosis method, aims to detect high grade urothelial carcinoma with a high specificity but low sensitivity, especially for detecting low-grade tumors. With advancements in molecular techniques, urine based liquid biopsy, artificial intelligence, and the growing interest in precision cytopathology, identification of urinary biomarkers for effective cancer screening, diagnosis, risk stratification, and therapeutic response monitoring has been a key focus of bladder cancer research and clinical practice guideline development. Urine allows noninvasive access to morphological, transcriptomic, epigenetic, and genomic materials from exfoliated cells in contact with tumor tissue. This review offers a comprehensive evaluation of the current utility of urinary biomarkers and technological innovations in cancer diagnosis and minimal residual disease detection. We also discuss the challenges and prospects for integrating molecular cytopathology into daily clinical practice.