Automated urine analysis of atypical urothelial cells for urothelial carcinoma: a prospective study
Maximilian Reimann, Thorsten Schlomm, Nathalie Winkler, Jeutner Jonathan, Jodie Maksoud, Ardita Aleti, Kai Kappert, Katharina Friedrich, Amir JahicObjectives
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.