Diagnosis

Could a Urine Test Refine Hematuria Evaluation?

Microscopic hematuria is common, but only a small proportion of patients undergoing evaluation will ultimately be diagnosed with bladder cancer. The challenge for urologists is identifying which patients are most likely to benefit from invasive evaluation without missing clinically significant disease. A prospective, international study suggests that a multi-protein urinary biomarker assay may provide additional information for risk stratification, particularly for detecting high-grade and muscle-invasive bladder cancer.

The study enrolled adults with microscopic hematuria considered at intermediate or high risk who were undergoing bladder cancer evaluation at nine centers in the United States and Japan. Of 321 participants enrolled between 2018 and 2025, 292 were eligible for analysis. Each provided a urine sample before undergoing cystoscopy, which served as the diagnostic reference standard along with biopsy when indicated. Researchers compared a 10-protein urinary biomarker assay with urine cytology and a single-analyte urinary test.

Bladder cancer was identified in 22 patients, representing 7.5% of the study population. The multi-protein assay demonstrated 82.0% sensitivity and a negative predictive value of 97.5% for detecting bladder cancer. By comparison, sensitivity was 44.8% for urine cytology and 9.3% for the single-analyte assay, while negative predictive values were 97.2% and 95.4%, respectively. These findings suggest that combining multiple urinary protein signals may provide greater sensitivity than relying on a single biomarker.

Performance was particularly notable for more aggressive disease. The multi-protein assay demonstrated 93.5% sensitivity for high-grade bladder cancer and detected all muscle-invasive cancers identified in the study. Cytology demonstrated 60.1% sensitivity for high-grade disease and 73.9% sensitivity for muscle-invasive disease. The findings are clinically relevant because the potential value of a urinary test depends not only on detecting cancer overall, but also on its ability to identify disease that would carry the greatest consequences if missed.

The results support continued investigation of urinary biomarkers as an additional tool for evaluating microscopic hematuria, but they do not establish a replacement for cystoscopy. Only 22 cancers were identified in the 292-patient cohort, making validation in larger populations important before such results could be used to alter established diagnostic pathways. For urologists, the broader opportunity may be using noninvasive molecular information alongside conventional risk factors to better determine who requires invasive evaluation while potentially reducing unnecessary procedures in patients at lower risk.