Latest developments in urinary tumor DNA and its current clinical role in urothelial bladder cancer and upper tract urothelial carcinoma.

Urinary tumor DNA (utDNA) has emerged as a promising noninvasive biomarker that may complement or reduce the need for cystoscopies in the diagnosis, surveillance, and treatment monitoring of urothelial carcinoma. Unlike plasma circulating tumor DNA (ctDNA), which is heavily diluted by hematopoietic cell-derived DNA, utDNA originates directly from tumor cell shedding into urine and often appears at higher concentrations, improving molecular detection. While there is an increasing number of publications using utDNA with promising results, most of these studies were developed from a laboratory perspective, making it difficult to find a direct clinical application. This review aims to apply a clinical perspective for potential daily practice use of utDNA testing.

This review summarizes the most recent literature on the potential clinical use of utDNA for diagnosis, follow-up, and response to treatment in nonmuscle-invasive bladder cancer, muscle-invasive bladder cancer, and upper tract urothelial carcinoma.

There is accumulating evidence on the potential use of utDNA for the diagnosis of urothelial carcinoma in the bladder as well as in the upper tract, while preliminary studies show promising results with sensitivities around 80-90% and specificities 90-100%, further research is needed.

Current opinion in urology. 2026 Mar 04 [Epub ahead of print]

Daniel A González-Padilla, José Daniel Subiela, Félix Guerrero-Ramos, Renate Pichler, Daniel Sánchez-Zalabardo, Felipe Villacampa-Auba

Department of Urology, Kidney and Bladder Cancer Unit, Clínica Universidad de Navarra., Department of Urology, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá., Department of Urology, Hospital Universitario 12 de Octubre., Department of Urology, Comprehensive Cancer Center Innsbruck (CCCI), Medical University of Innsbruck, Innsbruck, Austria., Department of Urology, Kidney and Bladder Cancer Unit, Clínica Universidad de Navarra, Pamplona, Spain.