Recent advances in liquid biopsy for genitourinary cancers: A narrative review.

BACKGROUND

Genitourinary (GU) malignancies remain a global health challenge. While tissue biopsy is the diagnostic gold standard, its invasive nature and inability to fully capture tumour heterogeneity or minimal residual disease (MRD) highlight the need for non-invasive alternatives. Liquid biopsy, analysing tumour-derived material in plasma or urine, has emerged as a promising tool for diagnosis, surveillance and response monitoring.

METHODS

PubMed was searched to identify studies on liquid biopsy in GU cancers. Eligible studies reported diagnostic or prognostic performance of assays using circulating tumour DNA (ctDNA), urinary tumour DNA (utDNA), extracellular vesicles or RNA. Reviews and case reports were excluded. Articles were screened independently by three reviewers using Rayyan.Ai, with evidence synthesised narratively.

RESULTS

In bladder cancer, utDNA-based assays-including methylation panels (BladMetrix, Bladder CARE), mutation assays (UroMuTERT) and capture-based sequencing-consistently achieved sensitivities of 80%-94% and specificities of 85%-95%, outperforming urine cytology and enabling detection of tumours years before clinical diagnosis. In upper tract urothelial carcinoma, utDNA methylation and mutation analysis demonstrated sensitivities of 80% and specificities up to 95%. In kidney cancer, ctDNA levels are relatively low; however, cell-free DNA methylation signatures (VHL, RNF185, RASSF1A) and cfMeDIP-Seq approaches have shown strong discriminatory power, with plasma-based assays achieving near 100% sensitivity in small studies. In prostate cancer, urinary RNA (PCA3, TMPRSS2:ERG), miRNA and metabolite-based assays achieved sensitivities and specificities ranging from 70% to 95%, with composite multigene panels (MyProstateScore2, utLIFE-PC) improving risk stratification beyond PSA alone.

CONCLUSIONS

Liquid biopsy demonstrates strong diagnostic and prognostic potential across GU cancers. While bladder and prostate cancer assays are most advanced, emerging evidence in UTUC and kidney cancer is encouraging. Prospective, longitudinal validation remains essential before widespread clinical adoption.