A Urine-Based Methylation Test for Bladder Cancer — Expert Commentary

Early identification of bladder cancer (BC) is critical for improving clinical outcomes. Developing urine-based molecular biomarkers is an area of active research. A recent study published in Urologic Oncology: Seminars and Original Investigations described a urine-based methylation analysis of TWIST1, NID2, RUNX3, GATA4, and FOXE1 in urinary cell pellet DNA as a biomarker.

The investigators examined the collected urine samples from 313 patients using a 2:1 ratio in a case-control setting from Canada and Switzerland. The study included 211 BC patients, including 180 patients with non-muscle invasive disease) and 102 controls. They used MethyLight, a real-time PCR assay to measure DNA methylation. All methylated genes significantly predicted BC vs. no BC and high grade vs. low grade (all P < 0.05) in univariate analyses. However, in multivariable analysis, only NID2, TWIST1 methylation, and age were independent predictors of BC (all P < 0.05). The sensitivity of NID2 and TWIST1 to predict BC and BC grade was 76.2% and 77.6%, respectively, whereas specificity was 83.3% and 61.1%. The area under the receiver operating characteristics curves for predicting BC overall and discriminating between high-grade and low-grade BC reached area under the receiver operating characteristics curves of 0.89 and 0.78, respectively.

This study is a significant addition to the growing literature reporting the use of urine-based tests of genomic alterations, including mutations and copy-number alterations and gene methylation as diagnostic, prognostic, or predictive biomarkers. Urine-based tests are poised to change clinical practice in the next few years across the clinical spectrum of BC patients.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine


  1. Hermanns T, Savio AJ, Olkhov-Mitsel E, et al. “A noninvasive urine-based methylation biomarker panel to detect bladder cancer and discriminate cancer grade.” Urol Oncol. 2020 Feb 18. pii: S1078-1439(20)30008-9. doi: 10.1016/j.urolonc.2020.01.007. PMID: 32081560
email news signup