Specificity of a Urine-Based PENK Methylation Test (EarlyTect Bladder Cancer) in Patients With Benign Urologic Conditions and Healthy Controls

Bladder cancer (BC) diagnosis relies primarily on cystoscopy and urine cytology. Although cystoscopy is the gold standard, it is invasive and costly, and urine cytology, although noninvasive, has limited sensitivity. EarlyTect Bladder Cancer (EarlyTect BC), a urine-based assay that detects proenkephalin methylation using real-time polymerase chain reaction, has been developed as a noninvasive diagnostic tool for patients with hematuria. However, its clinical specificity in populations without hematuria has not been fully evaluated. We evaluated 168 participants, including 112 healthy individuals and 56 patients with benign urologic diseases (BUDs), such as benign prostatic hyperplasia, urinary tract infection, and urinary stones. EarlyTect BC demonstrated an overall specificity of 98.2% (165 of 168), with specificities of 97.3% (109 of 112) in healthy individuals and 100% (56 of 56) in patients with BUDs. No subgroup differences were observed by age, sex, or disease type. These findings indicate that EarlyTect BC has a low false-positive rate in selected nonhematuria populations without known bladder cancer. Because this brief report evaluated specificity only and did not include patients with bladder cancer or a uniform reference standard, the findings should be interpreted as supportive evidence for clinical specificity rather than as evidence of overall diagnostic accuracy.