Diagnostic performance and pathologic associations of the UroVysion assay in patients with upper tract lesions and negative urinary cytology: a large-scale real-world study of 1,256 patients

PURPOSE: The UroVysion assay is widely used for diagnosing upper tract urothelial carcinoma (UTUC), but its value in patients with negative urinary cytology remains unclear. This study evaluated its diagnostic performance and pathological associations in this specific population. METHODS: This retrospective study included 1,256 patients with upper tract lesions on imaging, negative urinary cytology, and preoperative UroVysion testing. Pathological diagnosis served as the reference standard. Diagnostic performance was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Logistic regression analysis was used to evaluate the association between UroVysion positivity and high-grade disease, lymphovascular invasion (LVI), and muscle invasion (≥ pT2). Subgroup analyses were performed according to tumor size and location. RESULTS: Among the 1,256 patients, 1,007 (80.2%) had UTUC and 249 (19.8%) had benign lesions. The UroVysion assay showed a sensitivity of 66.9%, specificity of 82.7%, PPV of 94.0%, and NPV of 38.2%, and an overall accuracy of 70.1% for UTUC diagnosis. UroVysion positivity was independently associated with high-grade disease (OR = 2.10, p < 0.001), LVI (OR = 1.63, p = 0.023), and muscle invasion (OR = 1.32, p = 0.049). Interaction tests showed no significant heterogeneity by tumor size or tumor location. CONCLUSION: In patients with upper tract lesions and negative cytology, the UroVysion assay provides complementary diagnostic information and is associated with adverse pathological features. No significant heterogeneity in these associations was observed according to tumor size or location.