A Urinary Biomarker to Triage Patients for Cystoscopy in Patients with Microhematuria - Expert Commentary

Microscopic hematuria is one of the earliest clinical signs of urothelial carcinoma (UC), yet many patients do not undergo cystoscopic evaluation, thus delaying diagnosis. However, because the rate of UC in low-risk patients is 0.8%, cystoscopy is unsuitable as a screening tool. Accordingly, there has been interest in developing an accurate, safe, non-invasive urinary biomarker. A recently developed biomarker is Cxbladder Triage (CxbT), which combines the mRNA expression of five genes and four clinical questions to generate a risk score for UC. Lotan et al. recently evaluated the use of CxbT in determining whether cystoscopy was needed in lower-risk patients referred for microhematuria.

Eligible patients were stratified into lower risk (LR) and not lower risk (NLR), whereby the former was defined as a smoking history of 10 packs or less per year, no current gross hematuria, and urine microscopy with 3 to 29 red blood cells per high-power field. The final cohort had 390 patients, 255 of whom were classified as NLR. The median age was 62, and 53.7% of patients were male. Of the patients in the NLR group, 82% proceeded to cystoscopy, and 22 tumors were found (10.5%). The 135 LR patients were randomized to a control group (n = 54) and a test group (n = 81). In the test group, results from the CxbT test were provided before the decision for cystoscopy. The CxbT negative rate was 87.7%, while the overall test negative rate was 63%. The proportion of patients who opted for a cystoscopy was 19.7% in the test-negative group and 80% in the test-positive group. There was a 59% reduction in the number of patients undergoing cystoscopy in the test arm versus the control arm of the LR group. Overall, 43% of patients in the LR category had cystoscopy and one tumor was found (1.7%) in a patient who had a positive CxbT result. In patients who had a CxbT result and underwent a cystoscopy, the sensitivity rate of CxbT for UC was 90% (95% CI, 70 – 90). The specificity was 56% (95% CI, 49 – 56), the negative predictive value (NPV) was 99% (95% CI, 95 – 100), and the positive predictive value (PPV) was 15% (95% CI, 9 – 22). For high-grade disease, sensitivity was 100% (95% CI, 78 – 100), specificity was 56% (49 – 62), NPV was 100% (97 – 100), and PPV was 12% (7 – 19). For the subset of LR patients who had both the CxbT and cystoscopy (n = 75), sensitivity was 100% (3 – 100), specificity was 77% (66 – 86), NPV was 100% (94 – 100), and PPV was 5.6% (0.1 – 27.3).

The CxbT test led to a significant reduction in the rate of cystoscopy and, therefore, represents an avenue for evaluating patients with microhematuria while avoiding unnecessary cystoscopies. One limitation of this study is the need for serial follow-ups of patients who chose not to have cystoscopy and who did not return for follow-up evaluations, precluding the collection of repeat CxbT values over time. Future studies should be conducted using the risk categories mirroring the new AUA guidelines.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Lotan Y, Daneshmand S, Shore N, et al. A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria: The Safe Testing of Risk for Asymptomatic Microhematuria Trial. J Urol. 2024;212(1):41-51. doi:10.1097/JU.0000000000003991
Read the Abstract 

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AUA 2024: A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients with Microhematuria: The STRATA: Safe Testing of Risk for Asymptomatic Microhematuria Trial


Bridging the Gap in Microhematuria Evaluation: A Discussion on the STRATA Trial - Yair Lotan