Dynamic Precision Oncology for Real-Time Molecular Monitoring and Management in Urothelial Carcinoma

Abstract

The management of urothelial carcinoma (UC) is undergoing a paradigm shift from static anatomical staging to molecularly guided dynamic approaches that integrate time as a critical therapeutic variable. This evolution is driven by liquid biopsies, particularly circulating tumor DNA, which allow real-time tumor interrogation. We conducted this expert review to synthesize landmark evidence, enabling technologies, and implementation challenges in dynamic precision oncology for UC. In this non-systematic narrative review, we searched PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library for articles published between January 2015 and February 2026. Studies were selected based on their relevance to dynamic precision oncology, clinical actionability, and translational implementation, prioritizing landmark randomized controlled trials providing level 1–2 evidence, large prospective cohorts, and key translational studies. Enfortumab vedotin plus pembrolizumab established the new first-line standard for metastatic UC, achieving a median overall survival of 33.8 months versus 15.9 months (hazard ratio [HR] 0.51, 95% confidence interval 0.43–0.61). Circulating tumor DNA demonstrates robust prognostic value for molecular residual disease (MRD) detection (Level 2a evidence), stratifying recurrence risk with hazard ratios of approximately 4.5. Critically, the IMvigor011 trial has now provided Level 1b evidence that ctDNA-guided adjuvant atezolizumab improves both disease-free survival (DFS) (HR 0.64, p = 0.0047) and OS (HR 0.59, p = 0.0131) in ctDNA(+) patients, while validating treatment de-escalation in ctDNA(−) patients (1-year DFS 95%). Erdafitinib in patients harboring FGFR2/3 alterations (HR 0.64) confirms the value of genomic profiling. Major limitations include the inherent selection bias of this non-systematic approach, substantial platform heterogeneity, and lack of standardization. In conclusion, dynamic precision oncology has transformed UC management, with the IMvigor011 trial establishing ctDNA-guided MRD status as the first phase 3-validated predictive biomarker framework for adjuvant therapy selection in a solid tumor. Implementation requires adherence to established standardization frameworks, cross-platform and cross-agent validations, and tiered implementation strategies to ensure equitable access across diverse resource settings.