Automated urine analysis of atypical urothelial cells for urothelial carcinoma: a prospective study

OBJECTIVES: To prospectively evaluate the diagnostic value of atypical urothelial cells (Atyp.C), an automatically determined quantitative parameter of the Sysmex UF-5000 urine particle analyser (Sysmex Corp., Kobe, Japan), as a non-invasive biomarker for urothelial carcinoma (UC). Early diagnosis of UC remains challenging despite advances in diagnostic techniques. While non-invasive urine cytology has high diagnostic value, clinical evidence for Atyp.C in urine remains unclear. Quantification of Atyp.C in urine may improve non-invasive UC disease diagnostics. PATIENTS AND METHODS: Urine samples from 234 patients who underwent invasive urological intervention for non-malignant conditions (control group [CG]) or UC (intervention group [IG]) were considered. Based on histopathology, the IG was subclassified into low-grade (LG) and high-grade (HG) UC and was further grouped into non-muscle-invasive (non-MI) and MI UC. Patients who received neoadjuvant chemotherapy were analysed separately. Atyp.C of ≥0.1 Atyp.C/μL were defined as positive and were automatically quantified using the Sysmex UF-5000 urine particle analyser, which classifies epithelial cells with disproportionately high nucleic acid content relative to cell size. Smoking state, urinary tract infection (UTI), and micro-/macrohaematuria, were evaluated as potential confounding factors. Receiver operating characteristic (ROC) analysis was performed to assess explorative diagnostic Atyp.C performance. RESULTS: The Atyp.C concentration was higher in the IG than in the CG (mean [SEM] 0.53 [0.1] vs 0.29 [0.1] Atyp.C/μL; P = 0.004), with a sensitivity of 0.59. HGUC exhibited higher Atyp.C levels (mean [SEM] 0.85 [0.2] Atyp.C/μL, P < 0.001) and a sensitivity of 0.73. MI UC showed the highest Atyp.C concentrations (mean [SEM] 0.95 [0.4] Atyp.C/μL; P = 0.004) and sensitivity of 0.78. ROC analysis demonstrated the highest diagnostic accuracy for MI UC (area under the ROC curve = 0.75). ROC analysis was exploratory and lacked external validation. UTI was a significant confounder for Atyp.C quantification. CONCLUSION: The Atyp.C are elevated in HGUC, particularly in MI disease, supporting their potential as a non-invasive diagnostic biomarker in UC condition.