A urine-based DNA test could help identify which patients with hematuria require urgent cystoscopy while allowing lower-risk patients to undergo the invasive procedure later, according to a prospective, multicenter UK study. The GALEAS Bladder assay detected 71 of 77 bladder cancers and had a negative predictive value of more than 99 percent.
Cystoscopy remains central to investigating hematuria, or blood in the urine, but most patients referred for the procedure do not have bladder cancer. The procedure is invasive, requires an in-person appointment, and places substantial demands on clinical services.
In a study published in European Urology Oncology, researchers evaluated whether molecular testing could provide an additional way to determine which patients need the most rapid investigation. GALEAS Bladder uses next-generation sequencing to look for mutations associated with bladder cancer in DNA extracted from urine. The assay targets more than 450 variants across 23 genes.
The study enrolled patients referred for urgent hematuria investigation at seven UK National Health Service urology departments. Results from both the urine test and standard diagnostic investigations were available for 964 participants, 77 of whom had pathology-confirmed bladder cancer.
Importantly for diagnostic triage, the assay detected all 17 muscle-invasive cancers and 35 of 36 high-grade cancers. Six cancers were missed, all of which were non–muscle-invasive tumors. Among 887 patients without bladder cancer, 816 tested negative. Overall positive predictive value was 50 percent, compared with a negative predictive value exceeding 99 percent.
Modeling suggested that using the urine test to guide urgency could reduce the number of immediate cystoscopies substantially. At a prespecified decision threshold of 5 percent, the approach produced a net reduction of 730 urgent cystoscopies per 1000 patients compared with performing urgent cystoscopy in everyone, without reducing overall clinical benefit.
The findings support a potential role for molecular testing as a triage tool rather than a replacement for cystoscopy. A negative result could support deferred cystoscopy with appropriate surveillance, while a positive result could prioritize patients for prompt cystoscopy and histopathologic confirmation.
One limitation of this industry-sponsored study was incomplete follow-up for patients with positive molecular results but negative standard investigations. The authors note that randomized evidence would be required before urinary biomarkers could be recommended as replacements for cystoscopy.
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