Revolutionizing Hematuria Diagnosis: The CxBladder Triage Plus Test's Breakthrough Validation
A groundbreaking study has validated the CxBladder Triage Plus Test's diagnostic prowess in identifying patients with hematuria at high risk for urothelial carcinoma. This innovative test, as detailed in the Urologic Oncology journal, surpasses existing urine-based assays in assessing hematuria risk.
The CxBladder Triage Plus Test, a sophisticated diagnostic tool, builds upon the CxBladder Detect+ test by integrating mRNA expression of five known biomarkers and six DNA SNPs from FGFR3 and TERT. This comprehensive approach enables the test to stratify patients into low-risk, intermediate-risk, or high-risk categories for urothelial carcinoma, all based on a threshold of 0.15.
The DRIVE study, a multicenter, prospective observational study, involved 615 adult patients presenting with hematuria (278 with gross hematuria and 337 with microhematuria) at Veterans Affairs clinics. The study's findings revealed that 48 patients (7.8%) had histologically confirmed urothelial carcinoma, comprising 35 high-grade or carcinoma in situ tumors and 13 low-grade tumors.
The Triage Plus Test demonstrated impressive diagnostic performance, with a sensitivity of 94%, specificity of 77%, positive predictive value (PPV) of 26%, negative predictive value (NPV) of 99.3%, and a test-negative rate (TNR) of 71%. These results were consistent across patients with gross or microhematuria.
Furthermore, the Triage Plus Test outperformed earlier CxBladder assays. It exhibited higher specificity, PPV, and TNR compared to the Triage test, while showcasing higher sensitivity and NPV compared to Detect. When evaluated at a higher threshold (0.54), the test maintained its effectiveness, with a sensitivity of 60%, specificity of 95%, PPV of 51%, NPV of 96.4%, and TNR of 90%.
The study also highlighted the Triage Plus Test's ability to identify patients requiring further evaluation. Using the 2025 AUA MH risk stratification and GH status criteria, 97.4% of patients were deemed in need of additional assessment, with 5.3% classified as low-risk and 15.3% as intermediate risk. Interestingly, all 48 urothelial carcinoma cases were accurately classified using this broad classification, albeit with a PPV of only 8.0%.
Conversely, the Triage Plus Test effectively ruled out 70.9% of patients from further evaluation, with 99.3% of these patients subsequently having normal cystoscopy results. The test missed three tumors, one high-grade and two low-grade. Overall, the Triage Plus Test yielded a PPV of 26.3%, representing a 3.3-fold improvement over the 2025 AUA MH risk stratification (PPV of 8.0%).
However, the authors emphasized the need for further research with diverse patient populations to enhance the test's generalizability. They also stressed the importance of ongoing data analysis to optimize the assay's development and utilization.
In conclusion, the CxBladder Triage Plus Test's validation in a multicultural Veterans patient population is a significant advancement in hematuria diagnosis. It offers a promising opportunity for patients to bypass costly and uncomfortable hematuria evaluations, paving the way for more efficient and accurate risk assessment in urothelial carcinoma.
