JU INSIGHT A Urine-based DNA Methylation Marker Test to Detect Upper Tract Urothelial Carcinoma

By: Alireza Ghoreifi, MD, Keck School of Medicine, University of Southern California, Los Angeles; Seyedeh-Sanam Ladi-Seyedian, MD, Keck School of Medicine, University of Southern California, Los Angeles; Paolo Piatti, PhD, Zymo Research Corp, Irvine, California, Pangea Laboratory LLC, Tustin, California; Yap Ching Chew, PhD, Zymo Research Corp, Irvine, California, Pangea Laboratory LLC, Tustin, California; Benjamin Jara, BS, Pangea Laboratory LLC, Tustin, California; Lucy Sanossian, BS, Pangea Laboratory LLC, Tustin, California; Jeffrey M. Bhasin, PhD, Zymo Research Corp, Irvine, California; Taikun Yamada, MS, Zymo Research Corp, Irvine, California, Pangea Laboratory LLC, Tustin, California; Gerhard Fuchs, MD, Keck School of Medicine, University of Southern California, Los Angeles; Sumeet Bhanvadia, MD, Keck School of Medicine, University of Southern California, Los Angeles; Rene Sotelo, MD, Keck School of Medicine, University of Southern California, Los Angeles; Andrew Hung, MD, Keck School of Medicine, University of Southern California, Los Angeles; Monish Aron, MD, Keck School of Medicine, University of Southern California, Los Angeles, Mihir Desai, MD, Keck School of Medicine, University of Southern California, Los Angeles; Inderbir Gill, MD, Keck School of Medicine, University of Southern California, Los Angeles; Siamak Daneshmand, MD, Keck School of Medicine, University of Southern California, Los Angeles; Gangning Liang, PhD, Keck School of Medicine, University of Southern California, Los Angeles; Hooman Djaladat, MD, MS, Keck School of Medicine, University of Southern California, Los Angeles | Posted on: 18 May 2023

Ghoreifi A, Ladi-Seyedian SS, Piatti P, et al. A urine-based DNA methylation marker test to detect upper tract urothelial carcinoma: a prospective cohort study. J Urol. 2023;209(5):854-862.

Study Need and Importance

Diagnosis and preoperative risk stratification of patients with upper tract urothelial carcinoma (UTUC) present distinct challenges given the limitations of currently available tools, such as urine cytology, cross-sectional imaging, and endoscopic biopsy. DNA methylation has emerged as a potential diagnostic and prognostic factor for several cancers, including urothelial carcinoma. Despite the advances in the role of these novel markers in urothelial bladder cancers, data on patients with UTUC are sparse. This prospective cohort study aimed to investigate the clinical performance of Bladder CARE, a new urine-based epigenetic test that includes a panel of 3 urothelial-specific methylation biomarkers, for the diagnosis of patients with UTUC.

What We Found

Comparing 50 patients with primary UTUC and no concomitant bladder cancer with 50 sex/age-matched cancer-free healthy individuals, we found that UTUC patients had significantly higher cancer risk, expressed by higher Bladder CARE Index (BCI) values. The sensitivity, specificity, positive predictive value, and negative predictive value of the Bladder CARE test for detecting UTUC were 96%, 88%, 89%, and 96%, respectively (see Figure). This was much higher than the urine cytology values that showed a sensitivity of 37%. In addition, a significant correlation was found between BCI values and tumor size.

Figure. Overview of the results of Bladder CARE test and urine cytology for the diagnosis of upper urinary tract carcinoma (UTUC). AUC indicates area under the curve.

Limitations

This was a single-center study with a relatively small sample size. Urine cytology was not available for 30% of patients. In addition, the control group could have been selected from patients with a common trait and negative workup rather than healthy individuals.

Interpretation for Patient Care

Bladder CARE is a noninvasive urine-based test for the diagnosis of UTUC with high sensitivity and negative predictive value. In addition, the sensitivity of this test is significantly higher than that of standard urine cytology. Future studies include a multi-institutional assessment to confirm it as a biomarker for UTUC.