From Cystoscopy to Tumor Genomics: Integrating Urinary Molecular Biomarkers into Personalized NMIBC Surveillance

Non-muscle-invasive bladder cancer (NMIBC) requires lifelong surveillance, traditionally based on repeated cystoscopy and urine cytology, which impose substantial physical, psychological, and economic burdens. Although urinary biomarkers have been extensively investigated as noninvasive alternatives for more than three decades, their potential for clinical adoption has remained largely unrealized. The maturity of validated urinary molecular biomarkers has created new opportunities to reconsider NMIBC surveillance strategies. The urgent question is how these biomarkers can be optimally integrated into clinical practice. We believe that the path forward lies in embracing the biological heterogeneity of NMIBC and tailoring surveillance accordingly. We discuss the emerging potential of clinically available molecular assays, including Bladder EpiCheck, Xpert Bladder Cancer Monitor, and UroDiag, to reduce reliance on routine cystoscopy in selected patients, and propose a practical framework for integrating the molecular biomarkers into tumor biology-based and risk-adapted NMIBC surveillance. We further explore the potential of next-generation liquid biopsy approaches, urinary tumor-derived DNA (utDNA) and urinary extracellular vesicles (uEVs), which may enable tumor genomics-informed residual disease detection and longitudinal monitoring. Rather than replacing cystoscopy, we support a transition from cystoscopy-centred to molecularly informed surveillance, in which the frequency and timing of cystoscopy could be tailored according to individualized clinical and molecular risk. We envisage next-generation liquid biopsy as a natural extension of this approach, representing a continuum from urinary molecular biomarker-guided cystoscopy reduction toward tumor genomics-informed utDNA- and uEV-based surveillance. Such a framework may provide a foundation for progressively more personalized NMIBC surveillance. Its potential to reduce patient burden, improve quality of life, facilitate earlier detection of clinically relevant recurrence, and enable more precise and less invasive monitoring, however, remains to be established through prospective clinical validation.