Noninvasive Urinary DNA Methylation Test Accurately Diagnoses Bladder Cancer

Urine cytology is commonly used as an adjunct diagnostic tool, but its clinical applicability is limited due to its reduced sensitivity in detecting low-grade tumors and the high incidence of false negatives. Early detection is vital to prevent muscle-invasive bladder cancer, which often necessitates radical cystectomy and significantly raises mortality risk. A noninvasive urinary DNA methylation test has now shown high sensitivity and specificity for detecting high-grade or invasive bladder cancer.

A prospective multicenter study led by researchers from the University of Ulsan College of Medicine (Seoul, Korea) assessed the performance of a urinary DNA methylation test (PENK methylation) and compared its diagnostic accuracy to the nuclear matrix protein 22 (NMP22) test and urine cytology. The study, conducted at 10 different sites, involved participants aged 40 and older with hematuria, who underwent cystoscopy within three months between March 11, 2022, and May 30, 2024. The primary outcomes of the study were the sensitivity and specificity of the urinary DNA methylation test for detecting high-grade or invasive bladder cancer. Secondary objectives included evaluating the test's accuracy for overall bladder cancer (across all stages and grades) and comparing its sensitivity and specificity with those of the NMP22 test and urine cytology.

When compared to the NMP22 test or urine cytology, the urinary DNA methylation test demonstrated significantly better sensitivity for detecting both high-grade or invasive bladder cancer and overall bladder cancer. The results, published in JAMA Oncology, revealed that the urinary DNA methylation test had a sensitivity of 89% for detecting high-grade or invasive bladder cancer, outperforming both the NMP22 test and urine cytology with high specificity. While the test exhibited an excellent negative predictive value, its positive predictive value was found to be less optimal. These findings suggest that the urinary DNA methylation test could be highly sensitive and specific for detecting high-grade or invasive bladder cancer.