Urine Methylation Test for Urothelial Cancer Diagnosis and Surveillance.

Authors

Yucai Wu, Wencong Han, Shengwei Xiong, Yuhui He, Shiming He, Lanlan Dong, Tingting Li, Zhihua Li, Xinfei Li, Ninghan Feng, Liqun Zhou, Qi Tang, Xiaoping Zhang, Weifeng Xu, Yanqing Gong, Xuesong Li

Published in

JAMA network open. Volume 9. Issue 9. Pages e2636786. Sep 01, 2026. Epub Sep 01, 2026.

Abstract

Urothelial carcinoma (UC) is characterized by frequent recurrence, and accurate noninvasive tests remain needed for early detection and postoperative surveillance.
To develop and validate a urine-based assay targeting AL021918.2 and vimentin (VIM) methylation for UC detection and postoperative surveillance.
This prospective, blinded, multicenter diagnostic study was performed at 3 tertiary medical centers in China. Samples were collected between December 1, 2021, and June 25, 2025. Consecutively enrolled adults with UC, benign urinary diseases, or nonurothelial malignant disease were included in a single-center training cohort, a 3-center validation cohort, and a prospective surveillance cohort. The surveillance cohort had a median follow-up of 6 months, completed December 13, 2023.
Urinary DNA methylation was assessed using quantitative methylation-specific polymerase chain reaction (PCR) analysis.
The primary outcomes were the sensitivity and specificity of the methylation assay for UC detection. Secondary outcomes included diagnostic performance according to tumor stage and grade and comparisons with urine cytology and fluorescence in situ hybridization (FISH).
This analysis included a total of 2307 participants, consisting of 643 in the training cohort (median age, 64 [IQR, 56-71] years; 494 men [76.8%]), 1620 in the validation cohort (median age, 67 [IQR, 61-73] years; 1129 men [69.7%]), and 44 with UC in the surveillance cohort (median age, 62 [IQR, 59-72] years; 32 men [72.7%]). The assay demonstrated sensitivities of 91.2% (95% CI, 87.6%-93.9%) in the training cohort and 90.8% (95% CI, 88.4%-92.8%) in the validation cohort and specificities of 90.0% (95% CI, 85.9%-93.2%) in the training cohort and 93.2% (95% CI, 91.3%-94.7%) in the validation cohort. In the training and validation cohorts, sensitivity remained high for Ta UC (79.6% [95% CI, 64.3%-89.7%] and 84.3% [95% CI, 77.8%-89.2%], respectively) and low-grade UC (86.4% [95% CI, 77.0%-92.5%] and 82.5% [95% CI, 75.7%-87.8%], respectively). Compared with urine cytology and FISH, the methylation assay demonstrated higher sensitivity while maintaining comparable specificity. After surgery, urinary methylation results were negative in 30 of 32 patients (93.8%) with positive preoperative results. During surveillance, the assay detected all 9 recurrences with a median lead time of 4.5 (IQR, 1.5-5.5) months before clinical confirmation and remained negative in 29 of 35 patients (82.9%) without recurrence.
In this diagnostic study, a noninvasive PCR-based assay showed high diagnostic accuracy for UC detection and identified all observed recurrences during surveillance. The assay may serve as an adjunct for UC diagnosis and postoperative surveillance.
Chinese Clinical Trial Registry Identifier: ChiCTR2300078302.

PMID:
42809283
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.