Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods

The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010‐2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring. What's new? Urine is a valuable source of liquid biopsy for cancer, with applicability particularly in the detection of different analytes and cancer types. Little is known, however, about consistency within urine liquid biopsy methods. Here, the authors investigated reporting of urine protocols in the literature and discuss future recommendations for standardization and clinical application. Analyses show that many publications do not report information on preanalytical parameters. Moreover, urine liquid biopsy was relevant for urogenital cancers as well as a variety of other malignancies. The findings have implications for optimizing the clinical application of urine liquid biopsy in cancer detection and monitoring.