Urine cell-free RNA for bladder cancer detection and treatment response prediction
In brief
Urine RNA test detects localized bladder cancer with 95% sensitivity at 90% specificity
In 683 urine samples, the cell-free RNA test detected localized bladder cancer with 95% sensitivity and 90% specificity, outperforming urine tumor DNA analysis. In pretreatment samples from 114 patients, immune and proliferation signals helped predict response to bladder-directed treatment, with an area under the curve of 0.93; prospective studies must confirm whether the test improves care.
- Journal
- Nature medicine (Q1)
- Published
- 2 October 2026
- Study design
- Unclassified
- Evidence level
- Level 5, Expert Opinion (CEBM 5)
- Authors
- Kevin J Liu, William Y Shi, Monica C Nesselbush, Nick A Phillips, Kathleen E Mach, Bogdan Luca, et al.
- PMID
- 42827132
- DOI
- 10.1038/s41591-026-04673-3
Why clinicians should know about it
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Abstract
Urine biomarkers promise to improve noninvasive detection and molecular characterization of genitourinary malignancies. Here we describe urine random priming and affinity capture of cell-free RNA (cfRNA) fragments for enrichment analysis by sequencing (uRARE-seq), a liquid biopsy method for urine cfRNA profiling, and apply it to 683 urine samples from patients with cancer and controls. Urine cfRNA contained transcripts from genitourinary tissues and, in patients with prostate, kidney or bladder cancer, tumor-derived transcripts. uRARE-seq demonstrated 95% sensitivity at 90% specificity for detecting localized bladder cancer. The method outperformed urine tumor DNA analysis and was unaffected by the presence of field-effect mutations. Urine cfRNA analysis also sensitively detected minimal residual disease and distinguished complete molecular responses after surgery from those after intravesical Bacillus Calmette-Guérin (BCG). Pretreatment urine from complete responders to BCG was enriched for T cell and other immune signatures, suggesting a preexisting antitumor immune response, whereas nonresponders showed higher expression of proliferation-related genes. In pretreatment urine from 114 patients, this biological difference enabled development of a biomarker predicting likelihood of response to BCG versus chemotherapy (area under the curve 0.93) that was strongly associated with risk of recurrence. Urine cfRNA analysis is therefore a promising biomarker approach for bladder cancer and potentially other urologic malignancies, although prospective studies are needed to assess its clinical utility.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.