The Potential of Urine Biomarkers: A New Horizon in Non-Invasive Cancer Detection and Monitoring


The concept of liquid biopsy has revolutionized cancer diagnosis and treatment monitoring. Unlike traditional tissue biopsies, which provide a limited snapshot of the tumor, liquid biopsies can better capture intratumor heterogeneity. They have the advantage of being minimally invasive or even noninvasive, with urine being a prime example of the latter. Urine collection is simple, can be done at home or in a clinical setting, and allows for serial sampling and multiomic analysis. Urine’s role in liquid biopsy is gaining traction across various cancer types due to these advantages​​. Urinary biomarkers fall into several categories: diagnostic, monitoring, predictive, and prognostic. Diagnostic biomarkers identify the presence of disease, monitoring biomarkers assess disease status or treatment response, predictive biomarkers forecast the likelihood of benefit or harm from a specific therapy, and prognostic biomarkers predict disease progression or recurrence. Urine has been primarily utilized for detecting diagnostic biomarkers, followed by prognostic, monitoring, and predictive biomarkers. The analytes detected in urine, including cell-free or cellular DNA and RNA, extracellular vesicles, proteins, and metabolites, highlight urine’s potential as a multiomic sample type, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and metallomics​​.

In a new expert opinion review published in the International Journal of Cancer by PhD graduate Stephanie Jordaens, Karen Zwaenepoel, Wiebren Tjalma, Christophe Deben, Koen Beyers, Vanessa Vankerckhoven, Patrick Pauwels, and led by Professor Alex Vorsters from the University of Antwerp conducted a comprehensive and systematic analysis of the current state of urine sampling as a liquid biopsy tool for noninvasive cancer research. They focused on exploring the use of urine in detecting various cancer types, examining the preanalytical parameters and methodologies employed in this emerging field. They reviewed a vast array of literature, searching through major health and life sciences databases, including PubMed and ISI Web of Science, covering publications from 2010 to 2022. From the eligible publications, they extracted data on various aspects such as study population characteristics, cancer types, urine preanalytics, analyte classes, isolation and detection methods, and the types of biomarkers used. They organized their findings to present a comprehensive overview of urine as a liquid biopsy tool, covering its application in different cancer types, the variety of biomarkers investigated, and the methods used in these studies.

According to the authors, a significant challenge in the field is the lack of standardization in preanalytical parameters like sample collection, preservation, and storage. Most publications in this area fail to report these critical parameters, even though they significantly impact biomarker stability and accuracy. When preservation methods are mentioned, ethylenediaminetetraacetic acid (EDTA) or commercial methods are commonly used. The presence of nucleic acid-hydrolyzing enzymes in urine necessitates careful consideration of preservation methods to prevent DNA degradation​​.

The authors discussed some interesting cancer-specific applications. For instance, in urological cancers, particularly prostate cancer (PCa) and bladder cancer, there have been significant advances in the use of urinary biomarkers. There are FDA-approved or CLIA tests available for these cancers, highlighting the clinical utility of urine-based biomarkers in this field​​. Whereas in urothelial cancer, various analytes like cells, DNA (cell-free and cellular), exosomes, metabolites, proteins, and RNA have been investigated. About 30% of the studies focused on protein biomarkers. Studies have shown that urinary cellular DNA in urothelial cancer originates from cancer cells shed directly into the urine​​. While in prostate cancer research a wide range of urinary biomarkers were explored, though there is limited information on urine type or preservation methods used in these studies​​. Additionally, the authors discussed current research on gynecological cancers, particularly cervical cancer, endometrial cancer, and ovarian cancer, has primarily focused on Human Papillomavirus (HPV) detection. The majority of these studies used commercially available methods or EDTA for preservation. According to the authors, first-catch urine samples offer higher accuracy in HPV detection compared to other types​​.

The review highlights the increasing interest in using urine as a noninvasive, easily accessible sample type for cancer detection and monitoring, expanding beyond traditional blood-based liquid biopsies. By pointing out the lack of standardization in preanalytical methods, the review highlights a critical gap in current research practices, suggesting that addressing these inconsistencies is essential for advancing the field. Moreover, the authors illustrated the versatility of urine biomarkers across a wide range of cancers, not limited to the urogenital tract. This broad applicability underlines the potential of urine biomarkers in advancing cancer diagnostics and personalized medicine. The detailed analysis of current practices and methodologies in the review serves as a valuable resource for guiding future research, aiding in the development of standardized protocols, and paving the way for clinical applications. The challenge ahead lies in standardizing methodologies and ensuring consistency across studies to fully realize the potential of urine biomarkers in clinical oncology. Furthermore, the review’s insights into the noninvasive nature, ease of collection, and the potential for serial sampling of urine biomarkers underscore their significance in improving cancer diagnosis, monitoring treatment responses, and possibly enhancing patient quality of life.

The Potential of Urine Biomarkers: A New Horizon in Non-Invasive Cancer Detection and Monitoring - Medicine Innovates

About the author

Stephanie Jordaens has obtained a professional bachelor degree Chemistry – Biochemistry at the Karel de Grote University College, an academic bachelor degree biochemistry and biotechnology at the University of Antwerp followed by a Master of Science degree in biochemistry and biotechnology in the molecular gene-technology with major in cell biology and physiology.

Stephanie joined Novosanis in August 2019 as Biomedical Scientist and Baekeland PhD student in collaboration with the University of Antwerp. The topic of her PhD is “Urine as liquid biopsy for cancer detection”.

About the author

Prof Alex Vorsters is a bio-engineer with postgraduate course on Tropical Veterinary Medicine. He got his PhD in 2016 on detection of HPV DNA in urine and monitoring the impact of HPV vaccination. He coordinates a research team that investigates the use of first void urine as a liquid biomarker source: in cervical cancer screening programs, for follow-up of HPV vaccination programs, and other genital tract infections in women. Since 2015 he coordinates the activities of the Human Papilloma Virus Prevention and Control Board ( and he is the co-principal Investigator of the Coalition to Strengthen the HPV Immunisation community (  For his innovative research in this new field, he obtained in 2021 an ERC grant from the European Union.


Jordaens S, Zwaenepoel K, Tjalma W, Deben C, Beyers K, Vankerckhoven V, Pauwels P, Vorsters A. Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods. Int J Cancer. 2023;152(10):2186-2205. doi: 10.1002/ijc.34434.

Go To Int J Cancer.