What question did this study set out to answer?

This research aims to review the role of circulating tumor DNA (ctDNA) in urothelial carcinoma and its clinical applications.

June 11, 2026

The evolving landscape and clinical utility of circulating tumor DNA across the spectrum of urothelial carcinoma: A systematic review and framework for clinical integration

Q: What does this research mean for the field?

Circulating tumor DNA (ctDNA) serves as a highly sensitive and clinically actionable biomarker across all stages of urothelial carcinoma for risk stratification, treatment monitoring, and recurrence detection, with detection rates increasing alongside disease advancement. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Points

This research aims to review the role of circulating tumor DNA (ctDNA) in urothelial carcinoma and its clinical applications.
Systematic search of PubMed retrieved 390 articles; 61 studies were included for ctDNA analysis in urothelial carcinoma.
Independent dual screening and stratification by disease stage (NMIBC, MIBC, mUC, UTUC) were conducted.
Pooled detection rates for ctDNA were calculated across stages of the disease.
ctDNA detection rates were significantly higher in advanced stages: NMIBC (53.2%), MIBC (47.6%), mUC (85.9%), UTUC (50.5%).
In MIBC, patients with positive ctDNA had worse overall survival (hazard ratio 6.3); negative ctDNA indicated excellent outcomes (98% OS at 18 months).
Post-surgical ctDNA monitoring achieved a sensitivity of 94%–100% for recurrence, with lead times of 96 to 131 days.

Abstract

Abstract Urothelial carcinoma (UC) is a significant global health challenge with heterogeneous clinical presentations from nonmuscle‐invasive to metastatic disease. Circulating tumor DNA (ctDNA) has emerged as promising noninvasive biomarker for risk classification, treatment monitoring and recurrence detection. Systematic searches of PubMed identified 390 articles; 61 met inclusion criteria for plasma ctDNA analysis in UC. Independent dual screening, Joanna Briggs Institute assessment, and stratification by disease stage (nonmuscle‐invasive bladder cancer NMIBC, muscle‐invasive bladder cancer MIBC, metastatic urothelial carcinoma mUC, and upper tract urothelial carcinoma UTUC) were performed. Simple pooled detection rates were calculated. ctDNA detection rates increased with disease advancement: NMIBC (53.2%), MIBC (47.6%), mUC (85.9%), and UTUC (50.5%). TERT promoter mutations predominated, followed by genomic alterations in TP53 . Assays varied widely across studies with next‐generation sequencing (22.4%) being most common. In NMIBC, ctDNA enabled risk stratification and recurrence detection. In MIBC, IMvigor010 demonstrated patients with positive ctDNA had worse overall survival (OS) (hazard ratio, 6.3); IMvigor011 showed that patients with negative ctDNA managed without adjuvant therapy had excellent outcomes (98% OS at 18 months). Post‐surgical monitoring achieved 94%–100% sensitivity for recurrence with 96‐ to 131‐day lead times. In mUC, KEYNOTE‐361 showed ctDNA reductions at 6 weeks predicted improved OS ( p 2% in UTUC predicted worse OS ( p < 10 –3 ). ctDNA is a critical precision oncology tool in UC management, with TERT mutations as the predominant alteration. Stage‐tailored strategies are emerging, including risk assessment in NMIBC, refining adjuvant decisions in MIBC, and treatment monitoring in mUC. Integration of ctDNA‐guided approaches should proceed alongside prospective validation to ensure safe and effective adoption.

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Cite This Study

Mehta et al. (Tue,) studied this question.

synapsesocial.com/papers/6a2a503380c8f91e7f39cd43 https://doi.org/https://doi.org/10.1002/cncr.70448

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