Urine Methylation Test Detects Urothelial Cancer With 90.8% Sensitivity

A urine-based DNA methylation assay targeting AL021918.2 and vimentin (VIM) detected urothelial carcinoma (UC) with sensitivity and specificity exceeding 90% in a multicenter validation cohort, according to a diagnostic study published in JAMA Network Open.

Investigators developed and validated the IUrisure test (Wuhan Ammunition Life-tech), which uses quantitative methylation-specific polymerase chain reaction (PCR) analysis, for UC detection and postoperative surveillance. The study authors noted that UC is characterized by frequent recurrence and that accurate noninvasive tests remain needed. The assay requires 1mL of whole urine without centrifugation.

The prospective, blinded phase 2 study was conducted at 3 tertiary medical centers in China and included 2307 participants: 643 in a single-center training cohort, 1620 in a 3-center validation cohort, and 44 patients with UC in a surveillance cohort. In the validation cohort, the assay achieved a sensitivity of 90.8% (95% CI, 88.4%-92.8%) and a specificity of 93.2% (95% CI, 91.3%-94.7%), the study's primary outcomes. Validation-cohort sensitivity was 84.3% for Ta tumors and 82.5% for low-grade UC.

In head-to-head comparisons, overall sensitivity for UC was 95.1% for the assay vs 45.1% for urine cytology, and 96.0% vs 61.4% for fluorescence in situ hybridization (FISH), with comparable specificity in small control groups. Specificity was slightly lower in patients with non-UC urinary system cancers than in those with benign urinary tract diseases (88.5% vs 92.8% in the validation cohort). During surveillance, the assay detected all 9 recurrences, with a median lead time of 4.5 months before clinical confirmation, and remained negative in 29 of 35 patients without recurrence.

The authors acknowledged that the surveillance cohort was relatively small and that short follow-up may have led to underestimation of specificity. They stated that randomized clinical trials comparing assay-assisted with standard cystoscopic surveillance are needed to validate the assay's clinical utility. The investigators concluded that the assay may serve as an adjunct for UC diagnosis and postoperative surveillance.

Source: Wu Y, Han W, Xiong S, et al. Urine methylation test for urothelial cancer diagnosis and surveillance. JAMA Netw Open. 2026;9(9):e2636786. doi:10.1001/jamanetworkopen.2026.36786