A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma: A Prospective Cohort Study
Alireza Ghoreifi, Seyedeh‐Sanam Ladi‐Seyedian, Paolo Piatti, Yap Ching Chew, Benjamin Jara, Lucy Sanossian, Jeffrey Bhasin, Taikun Yamada, Gerhard Fuchs, Sumeet Bhanvadia, René Sotelo, Andrew J. Hung, Monish Aron, Mihir Desai, Inderbir S. Gill, Siamak Daneshmand, Gangning Liang, Hooman Djaladat
Abstract
PURPOSE: We explored the accuracy of a urine-based epigenetic test for detecting upper tract urothelial carcinoma. MATERIALS AND METHODS: Under an Institutional Review Board-approved protocol, urine samples were prospectively collected from primary upper tract urothelial carcinoma patients before radical nephroureterectomy, ureterectomy, or ureteroscopy between December 2019 and March 2022. Samples were analyzed with Bladder CARE, a urine-based test that measures the methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and 2 internal control loci using methylation-sensitive restriction enzymes coupled with quantitative polymerase chain reaction. Results were reported as the Bladder CARE Index score and quantitatively categorized as positive (>5), high risk (2.5-5), or negative (<2.5). The findings were compared with those of 1:1 sex/age-matched cancer-free healthy individuals. RESULTS: Conclusions:Bladder CARE is an accurate urine-based epigenetic test for the diagnosis of upper tract urothelial carcinoma, with much higher sensitivity than standard urine cytology.