A review of the performance of urinary cytology with a focus on atypia, upper tract and updates on novel ancillary testing.

The Paris System for Reporting Urine Cytology (TPS) is remarkable for its high predictive value in the detection of high-grade urothelial carcinoma, especially of the bladder. However, universal compliance with TPS-recommended threshold for atypical call rates (15%) and TPS performance in the rarer upper tract urothelial carcinomas (UTUC) are challenging. UTUC diagnosis is compounded by instrumentation artifacts, degenerative changes superimposed on an ambiguous cytology, difficult-to-access location, lack of specific standardized criteria, and a limited number of UTUC-focused studies. We reviewed TPS-applied studies published since 2022, noting up to 50%, exceeding the suggested 15% threshold for atypia. Our examination of ancillary tests for UTUC explored novel approaches including DNA methylation analysis, the detection of overexpressed tumor-linked messenger RNAs, and immunohistochemistry on markers such as CK17. Preliminary evidence from our review suggests that ancillary tests display superior performance over cytology, including in voided samples and low-grade urothelial carcinoma. Importantly, voided samples obviate the risks of ureterorenoscopy. Finally, we explored the future opportunities offered by artificial intelligence and machine learning for a more objective application of TPS criteria on urine samples.