The Diagnostic Performance of Cxbladder Resolve, Alone and in Combination with Other Cxbladder Tests, in the Identification and Priority Evaluation of Patients at Risk for Urothelial Carcinoma. Issue 6 (5th December 2021)

• Record Type: Journal Article
• Authors: Raman, Jay D.; Kavalieris, Laimonis; Konety, Badrinath; Porten, Sima; Daneshmand, Siamak; Lotan, Yair; Loo, Ronald
• Is Part Of: Journal of urology. Volume 206:Issue 6(2021)
• Page Start: 1380
• Page End: 1389
• Publication Date: 2021-12-05
• Subjects: biomarkers -- hematuria -- predictive value of tests -- sensitivity and specificity -- urinary bladder neoplasms; Genitourinary organs -- Periodicals; Urology -- Periodicals; Urology -- Periodicals; Urologie -- Périodiques; Urologie; 616.6
• DOI: 10.1097/JU.0000000000002135
• Languages: English
• ISSNs: 0022-5347

Abstract

Abstract : Purpose: Cxbladder (Cxb) tests combine genomic biomarkers in urine with phenotypic and clinical data to classify hematuria patients into those at low/high probability of urothelial carcinoma (UC). Cxbladder Resolve (CxbR) is designed for use after Cxb Triage (CxbT) and Detect (CxbD), where CxbT-positive tests reflex to CxbD and CxbD-positive to CxbR to identify patients at high probability of high-impact tumors (HIT; high grade Ta, Tis or T1–T3). This study validated the diagnostic performance of CxbR in identifying HIT, and validated the algorithm of Cxb tests to segregate high-impact from low-impact tumors. Materials and Methods: CxbR was developed in 863 hematuria patients in 3 studies in United States, Australia and New Zealand. CxbR, separately and combined with other Cxb tests, was validated in a prospective, observational U.S. study in 548 hematuria patients. All UC diagnoses were confirmed by histopathology. Results: In the development data set, CxbR sensitivity was 92.4% (95% CI 83.3–96.7) and specificity 93.8% (95% CI 86.8–97.2) for identifying HIT within the high priority category. During external validation, sequential Cxb tests correctly ruled out 87.6% of patients from further workup (negative predictive value 99.4%); 100% of HIT were correctly identified (specificity 96.3%), and 3 low-grade tumors were missed. In both studies, all patients with HIT were correctly assigned to prioritized evaluation. Conclusions: CxbR has high sensitivity and specificity, correctly identifying all HIT. Sequential Cxb tests accurately segregate patients with a low vs high probability of HIT, focusing resources on those patients, with a diagnostic yield 4.8-fold higher than American Urological Association guideline stratification.