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

( The 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX between May 3 and May 6, 2024, was host to the Health Services Research, Value of Care: Cost and Outcomes Podium session. Dr. Yair Lotan presented the results of STRATA, a multicenter prospective randomized controlled trial comparing Cxbladder triage to cystoscopy in patients with microhematuria.

Dr. Lotan began his presentation by discussing the prevalence of microhematuria in adults, noting that approximately 7 million patients annually present with this condition. However, he highlighted that the incidence of urothelial carcinoma associated with microhematuria is relatively low, ranging between 1-5%. Despite this, a significant proportion of patients evaluated for microhematuria undergo unnecessary cystoscopies.

The investigators hypothesized that in a prospective randomized trial, having the results of the Cxbladder triage (CxbT) result would significantly reduce the number of cystoscopies done in the context of low-risk hematuria patients.

The primary outcome of this trial was:

  • To compare the rate of cystoscopy using standard of care compared to an alternative clinical pathway using the CxbT to risk stratification of low-risk microhematuria patients.

Secondary outcomes included:

  • Evaluation of accuracy measures (Sensitivity, specificity, NPV, PPV) of CxbT in patients enrolled in the study and who had a cystoscopy performed.

Dr. Lotan outlined the study design, wherein all patients with hematuria underwent urine testing with Cxbladder triage (CxbT) and were classified into two risk categories:

  • Lower risk: 3-29 red blood cells/high power field (RBC/hpf) and minimal smoking history (<10 packs years).
  • Not lower risk: >30 RBC/HPF or >10 pack-year smoking history.

Patients categorized as lower risk were then randomized into two groups: one receiving the CxbT results and the other receiving standard care (cystoscopy). Patients with negative CxbT results were offered the option to forego cystoscopy and instead undergo follow-up surveillance. Patients in the not-lower-risk group also underwent CxbT but received standard care testing regardless. Demographic characteristics of the patients are presented in the table below:

The patients on the lower risk were randomized to testing with CxbT or standard of care. In the test arm, patients were approached according to their CxbT results: if negative they were offered omission of cystoscopy and follow-up surveillance, if positive they were offered standard of care. Patients in the not-lower-risk group had a CxbT but underwent standard-of-care testing. Demographic characteristics of the patients are presented in the table below:STRATA_trial_demographics.jpeg
A total of 135 patients were recruited into the low-risk arm, with 81 assigned to the test arm (CxbT) and 54 to the control arm. In the test arm, the negative rate of CxbT was 88% (71/81), out of which 57 patients opted not to undergo cystoscopy, while 14 (20%) chose to proceed with cystoscopy. Among those with a positive CxbT result, the majority (8 out of 10) underwent cystoscopy. A notable relative reduction in cystoscopy rates of 59% was observed between the control and test arms. Dr. Lotan also highlighted an unusual observation in the control arm, where 18 patients did not undergo cystoscopy, while 36 underwent cystoscopic evaluation, despite the study being conducted in academic centers.
Follow-up data were available for 367 patients, with a median follow-up time of 372 days from the initial visit. Among the 57 patients with lower risk (CxbT negative) who chose not to undergo cystoscopy, 48 had follow-up data. One patient, initially negative on CxbT, underwent another test 13 months later, which was positive. Subsequently, this patient underwent cystoscopy, confirming a single high-grade Ta tumor. In the not-lower-risk cohort, one patient had an initial negative cystoscopy, but a repeat cystoscopy 4 months later revealed a high-grade tumor (Tx).
Of the 270 evaluable patients, 22 had a confirmed tumor diagnosis. The sensitivity of the CxbT test was 90%, specificity 56%, negative predictive value (NPV) 99%, and positive predictive value (PPV) 15%.270 evaluable patients, 22 had a confirmed tumor diagnosis.
The investigators acknowledged some limitations of the study. Firstly, they noted that the willingness of low-risk patients to return for follow-up was significantly lower than anticipated. Additionally, since the study was designed before the 2020 microhematuria guidelines were published, patient stratification did not align with the new AUA guidelines risk stratification system outlined below. This misalignment could potentially result in some discordance in risk stratification between the study and the guideline's risk stratification system.
  2020 microhematuria guidelines 
Dr. Lotan concluded his presentation with the following affirmations: 

  • STRATA marks the first multicenter randomized controlled trial to compare a marker-based approach (CxbT) informing the decision for cystoscopy in patients with low-risk hematuria.
  • Cxbladder Triage resulted in a notable 59% relative reduction in cystoscopy rates.
  • The sensitivity of the CxbT test is 90% with a remarkable negative predictive value (NPV) of 99%, highlighting its efficacy as a triage test.
  • Cxbladder provides the most robust clinical utility evidence to date, supporting the potential inclusion of Cxbladder in future updates to the microhematuria guidelines.

Presented by: Yair Lotan, MD, Urologist, UT Southwestern Medical Center, Dallas, TX

Written by: Julian Chavarriaga, MD - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX between May 3rd and May 6th, 2024 

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A Multicenter Prospective Randomized Controlled Trial Comparing Cxbladder Triage to Cystoscopy in Patients With Microhematuria. The Safe Testing of Risk for Asymptomatic Microhematuria Trial