Urinary DNA Extraction in Uro-Oncology and Selected Non-Urological Malignancies: A Narrative Review

Urine is an attractive source of tumor-derived DNA because collection is non-invasive, repeatable, and compatible with large-volume or home-based sampling. Urinary DNA comprises biologically distinct fractions, principally cellular DNA from exfoliated cells and urinary cell-free DNA (cfDNA), which may originate from local release within the urinary tract or from transrenal passage of circulating DNA. Consequently, analytical performance is strongly influenced by urine collection, fractionation, stabilization, extraction, and downstream molecular analysis. This narrative review summarizes evidence from 58 studies addressing urinary DNA extraction and its application in oncology. Analytical studies, including experiments using healthy volunteers, synthetic DNA, and controlled laboratory conditions, demonstrate substantial differences between extraction platforms, particularly in the recovery of short and ultrashort cfDNA fragments. These findings establish analytical performance but should not be interpreted as evidence of clinical superiority. Clinical studies have subsequently demonstrated the feasibility of urinary DNA for mutation detection, methylation analysis, copy-number profiling, surveillance, and treatment-response monitoring, with the strongest evidence currently available in urothelial carcinoma. Applications have also been reported in selected non-urological malignancies. However, methodological standardization, prospective clinical validation, inter-laboratory reproducibility, control of biological and clinical confounders, demonstration of clinical utility, and cost-effectiveness remain necessary before urinary DNA analysis can be incorporated routinely into oncological practice.