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