There are currently six urinary assays approved by the US FDA for clinical use as an adjunct to cystoscopy. These are largely protein-based biomarkers and as a group, demonstrate higher sensitivity than urine cytology. However, they are plagued by limited sensitivity with low-grade tumors and a high rate of false positives. As such, many perceive the currently approved markers to be of very limited or no utility, particularly when used in isolation.
In recent years, there have been significant developments in the development of urinary biomarkers. In the protein biomarker sphere, the URO17™ test has very recently exhibited sensitivity for low-grade tumors while demonstrating a high degree of specificity. There is also increased recognition that combined use of biomarkers may augment sensitivity and specificity, and efforts in this area have mainly been in combining genetic and epigenetic alterations. In our review, we discuss the utility of multigene panels involving DNA, mRNA, and epigenetic targets. Of these, Cxbladder which quantifies mRNA biomarkers is arguably the most well known. However, we also provide a discussion of upcoming panels such as AssureMDx, Uromonitor®, and EpiCheck® which provide a novel approach investigating the role of methylation as a urinary biomarker.
From a practical standpoint, the review also devotes attention to practical issues surrounding the use of urinary biomarkers. We discuss how the type of urine collected, as well as variability in storage conditions, transport, and processing, may affect assay results – and hence the importance of an agreed standard operating procedure. The review also provides an overview of the practical value of urinary biomarkers, and how the potential benefit of urinary biomarkers depends on the situation in which it is employed.
Written by: Kenrick Ng, MD, Cancer Research UK Clinical Research Fellow and Specialist Registrar in Medical Oncology, UCL Cancer Institute, London, England, Twitter: @kenrickng1, and Nikhil Vasdev, MD, FRCS (Urol), Consultant Urological and Robotic Surgeon, Hertfordshire and Bedfordshire Urological Cancer Centre, Senior Clinical Lecturer, University of Hertfordshire, Hatfield, England, Twitter: @nikhilvasdevuro
- Ng, Kenrick, Arnulf Stenzl, Anand Sharma, and Nikhil Vasdev. "Urinary biomarkers in bladder cancer: A review of the current landscape and future directions." In Urologic Oncology: Seminars and Original Investigations. Elsevier, 2020.