Urine cytology suspicious for urothelial carcinoma: Prospective follow-up of cases using cytology and urine biomarker-based ancillary techniques.

Urine cytology results that are suspicious for urothelial carcinoma (UC) are challenging. The objective of this study was to elucidate the clinical significance of such results in patients who have a negative cystoscopy.

In this prospective study, 83 patients who had urine cytology that was suspicious of UC and a negative cystoscopy underwent a second cystoscopy and urine evaluation by cytology, UroVysion fluorescence in situ hybridization (FISH) assay, FGFR3 (fibroblast growth factor receptor 3) and TERT (telomerase reverse transcriptase) mutations and an 8-gene expression classifier (GEC). Results from all techniques were compared with patients' clinical outcomes.

The presence of tumor was identified in 41% of patients; of these, 82% had tumors identified at their second evaluation (76% high-grade [HG] tumors), and 18% had tumors identified at a later follow-up (50% were HG tumors). After The Paris System for Reporting urinary Cytology (TPS) reclassification, 53 cytology results still had an indeterminate diagnosis (13 were suspicious for HGUC, and 40 had atypical urothelial cells (AUCs)]. Complete results from second evaluations using urine cytology, cytology-TPS, FISH, and GEC were available for 6 cases that were suspicious for HGUC and 34 cases that had AUCs. The sensitivity of these techniques to detect HG tumors in cases that were suspicious for HGUC was 100%, except for cytology-TPS, for which the sensitivity was 50%. The sensitivity of cytology and cytology-TPS to detect HG tumors in cases with AUCs was 33%, whereas the sensitivity of fluorescence in situ hybridization and GEC in these cases was 83% and 75%, respectively, to detect HG tumors at the second evaluation.

The current results indicate the relevant clinical significance of indeterminate urine cytology findings and strongly suggest the use of complementary evaluations by urine biomarker-based, ancillary techniques to elucidate their significance.

Cancer cytopathology. 2020 Feb 21 [Epub ahead of print]

Ruth Montalbo, Laura Izquierdo, Mercedes Ingelmo-Torres, Pilar Galve, Manel Solé, Agustín Franco, María José Ribal, Antonio Alcaraz, Lourdes Mengual

Laboratory and Department of Urology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain., Department of Pathology, Hospital Clínic, Barcelona, Spain.