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THE DIAGNOSTIC PERFORMANCE OF CXBLADDER TRIAGE PLUS FOR THE IDENTIFICATION AND PRIORITY EVALUATION OF VETERANS AT RISK FOR UROTHELIAL CARCINOMA: THE DRIVE STUDY

T. Aboushwareb¹, S. Savage², T. Lough³, K. Sakamoto⁴

¹Pacific Edge Diagnostics, Clinical development, Hummelstown, United States
²Ralph H. Johnson Veterans Affairs Health Care System, Charleston, SC, USA;, Urology, Charelston, United States
³Pacific Edge Ltd, Clinical development, Dunedin, New Zealand
⁴San Diego VA Medical Center, San Diego, CA, USA, Urology, San Diego, United States

Introduction:

Cxbladder assays are diagnostic urinary biomarker assays that are used for risk stratification for the presence/absence of urothelial carcinoma (UC) among patients presenting with hematuria. Second-generation Cxbladder Triage Plus measures mRNA expression of 5 genes associated with UC, as well as 6 DNA single-nucleotide polymorphisms from FGFR3 and TERT. The DRIVE study evaluated the diagnostic performance of Triage Plus for UC in a Veterans Affairs (VA) population with hematuria.

Material and methods:

DRIVE was a multicenter, prospective, observational study that enrolled adults (≥18 years) from VA clinical centers with confirmed hematuria who were undergoing evaluation for possible UC. Patients provided midstream urine samples for testing using the Triage Plus assay. The primary objective was external clinical validation of the diagnostic performance of Triage Plus vs white light cystoscopy, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and test-negative rate (TNR). The gold standard for primary UC diagnosis was pathologic confirmation. The study was designed to achieve 80% power to establish that the lower bound of the 90% confidence interval (CI) for sensitivity was >85%.

Results:

Of 615 patients with hematuria (mean age 64.5 years, 90.9% male), 587 had available Triage Plus results. Based on Triage Plus results (score threshold 0.15), 171 patients had an intermediate or high UC risk (of whom 45 had confirmed tumors) and 416 patients were ruled out (of whom only 3 had confirmed tumors; false-negative rate of 0.7%; Table). Compared with the gold standard, Triage Plus had sensitivity of 94% (95% CI 83–99%), specificity of 77% (73–80%), PPV of 26% (20–34%), NPV of 99.3% (97.9–99.9%), and TNR of 71% (67–75%). The performance characteristics of Triage Plus were similar in patients with gross hematuria (n=267) or microhematuria (n=320). When compared with risk stratification by 2025 American Urological Association microhematuria guideline risk criteria or gross hematuria status, Triage Plus had a 3.25-fold (26%/8%) improvement in PPV.