Discov Oncol. 2026 Jul 19. doi: 10.1007/s12672-026-05594-w. Online ahead of print.
ABSTRACT
BACKGROUND: Hematuria is a common clinical presentation of bladder cancer (BC). Accurate non-invasive diagnostic tools are needed to complement or reduce the reliance on cystoscopy. In this study, we investigated the diagnostic performance of urinary exfoliated-cell chromosomal copy-number aberration detection (UroCAD), a novel assay utilizing low-coverage whole-genome sequencing (LC-WGS) to detect chromosomal instability (CIN) in exfoliated urothelial cells. The evaluation included the use of UroCAD alone and in combination with ultrasonography.
METHODS: A consecutive series of 153 patients with hematuria was prospectively enrolled. Urine samples were subjected to genome-wide copy-number variation (CNV) profiling using UroCAD. The diagnostic performance of UroCAD and ultrasonography, individually and in combination, was assessed using histopathology as the reference standard. Statistical analyses included receiver operating characteristic (ROC) curves, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy.
RESULTS: Of the 153 enrolled patients, 151 (113 with pathologically confirmed BC and 38 with benign lesions) were included in the final analysis. UroCAD alone showed a specificity of 78.9% and a PPV of 90.1%, with an area under the ROC curve (AUC) of 0.84 (95% confidence interval [CI]: 0.77-0.91). Ultrasonography alone exhibited higher sensitivity than UroCAD (67.0% vs. 64.6%), but lower specificity (59.5%). The “CIN OR ultrasound” rule achieved the highest sensitivity (85.7%) and overall accuracy (75.8%), with an NPV of 51.5%. The “CIN AND ultrasound” rule yielded the highest specificity (91.9%) and PPV (94.4%). The CNV burden was strongly associated with tumor stage, with higher-stage tumors showing more frequent and pronounced genomic instability.
CONCLUSIONS: UroCAD has potential as a non-invasive assay for BC detection. Combined with ultrasonography, it offers a dual-strategy approach: a high-sensitivity strategy (“CIN OR ultrasound”) that may help identify patients warranting further evaluation, although its low NPV precludes safe exclusion of malignancy; and a high-specificity strategy (“CIN AND ultrasound”) for confirmatory purposes. This synergistic strategy may aid in the risk stratification of patients with hematuria, although further prospective studies are required to validate its clinical utility. Trial registration ISRCTN Registry ISRCTN50547972 (http//www.isrctn.com/ISRCTN50547972). Registration date 27 April 2026.
PMID:42472409 | DOI:10.1007/s12672-026-05594-w