Renske D. M. Steenbergen

High cancer mortality rates and the rising cancer burden worldwide drive the development of innovative methods in order to advance cancer diagnostics. Urine contains a viable source of tumor material and allows for self‐collection from home. Biomarker testing in this liquid biopsy represents a novel approach that is convenient for patients and can be effective in detecting cancer at a curable stage. Here, we set out to provide a detailed overview of the rationale behind urine‐based cancer detection, with a focus on non‐urological cancers, and its potential for cancer diagnostics. Moreover, evolving methodological challenges and untapped opportunities for urine biomarker testing are discussed, particularly emphasizing DNA methylation of tumor‐derived cell‐free DNA. We also provide future recommendations for technical advancements in urine‐based cancer detection and elaborate on potential mechanisms involved in the transrenal transport of cell‐free DNA.