Study validates diagnostic performance of CxBladder Triage Plus Test

The CxBladder Triage Plus Test demonstrated clinical validity in identifying which patients with hematuria are at higher risk for urothelial carcinoma, according to findings from the observational DRIVE study (NCT04943380) published in Urologic Oncology.¹

The CxBladder Triage Plus is a diagnostic urinary biomarker assay that builds on the CxBladder Triage and Detect tests by combining “mRNA expression of 5 known biomarkers and 6 DNA SNPs from FGFR3 and TERT,” according to the authors. The test uses these features to risk stratify patients as either low-risk (below the 0.15 threshold) or intermediate- or high-risk (above the 0.15 threshold) for urothelial carcinoma.

The DRIVE study included adult patients who presented to Veterans Affairs clinics with gross hematuria or microhematuria. The diagnostic performance of the Triage Plus test was compared with white light cystoscopy as well as the 2025 American Urological Association (AUA) microhematuria (MH) risk stratification or gross hematuria (GH).

“These findings demonstrate the improved utility of the CX Bladder Triage Plus test over other urine-based assays, including AUA risk stratification, when assessing risk for hematuria patients,” said lead author Stephen J. Savage, MD, in correspondence with Urology Times®. “With shared decision-making, it can offer an opportunity for patients to bypass costly and uncomfortable hematuria evaluations. It is especially encouraging that this test was validated in a multicultural Veterans patient population with over 30% African American patients.”

In total, the study included 615 patients with hematuria, of whom 278 had gross hematuria and 337 had microhematuria. Of those, 48 patients (7.8%) had histologically confirmed urothelial carcinoma, which included 35 cases of high-grade or carcinoma in situ tumors and 13 cases of low-grade tumors.

In the overall cohort, 587 patients had Triage Plus Test results available for analysis. The test demonstrated a sensitivity of 94% (95% CI, 83% to 99%), specificity of 77% (95% CI, 73% to 80%), positive predictive value (PPV) of 26% (95% CI, 20% to 34%), negative predictive value (NPV) of 99.3% (95% CI, 97.3% to 99.9%), and a test-negative rate (TNR) of 71% (95% CI, 67% to 75%).

According to the authors, “These performance characteristics were similar in patients with GH or MH.”

The Triage Plus test also demonstrated improved diagnostic performance compared with the earlier CxBladder assays. Specifically, the Triage Plus test showed a higher specificity, PPV, and TNR compared with the Triage test, and higher sensitivity and NPV compared with Detect.

The investigators also assessed the Triage Plus test at a higher threshold (0.54), with a positive result indicating a higher risk of urothelial carcinoma. At this threshold, the test had a sensitivity of 60% (95% CI, 45% to 74%), specificity of 95% (95% CI, 93% to 97%), PPV of 51% (95% CI, 37% to 64%), NPV of 96.4% (95% CI, 94.5% to 97.8%), and TNR of 90% (95% CI, 88% to 93%).

Using the 2025 AUA MH risk stratification and GH status criteria, 97.4% of patients in this cohort were identified as needing further evaluation. This included 5.3% of patients classified as low-risk and 15.3% classified as intermediate risk.

The authors noted, “Using this broad classification, all 48 [urothelial carcinoma] cases were correctly classified, but with a PPV of only 8.0%.”

Conversely, the Triage Plus test “ruled out” 70.9% of patients from further evaluation, of whom 99.3% went on to have a subsequent normal cystoscopy. The test missed 3 tumors, 1 which was high-grade and 2 which were low-grade. Overall, the Triage Plus test yielded a PPV of 26.3%, which corresponded to a 3.3-fold improvement over that of the 2025 AUA MH risk stratification (PPV, 8.0%).
The authors did note that further work on diverse patient populations were still warranted to broaden the generalizability of the test.

“It will be important to see how the assay is utilized in the future and to ensure that, when adopted, there is minimal adverse impact,” Savage concluded. “As with many similar assays, it is very possible that increased data analysis will allow for further improvements in how the assay is developed and utilized.”

REFERENCE

1. Savage SJ, Ercole CE, Hemstreet G, et al. Diagnostic performance of Cxbladder Triage Plus for the identification and stratification of patients at risk for urothelial carcinoma: The multicenter, prospective, observational DRIVE study. Urol Oncol. 2025:S1078-1439(25)00405-3. doi:10.1016/j.urolonc.2025.10.008