Circulating Tumor DNA After Radical Cystectomy as a Marker of Minimal Residual Disease in Muscle-Invasive Bladder...

Muscle-invasive bladder cancer (MIBC) is characterized by high biological aggressiveness and a significant risk of recurrence after radical cystectomy. Conventional prognostic models are insufficient to detect minimal residual disease (MRD). Circulating tumor DNA (ctDNA) has emerged as a promising biomarker capable of identifying subclinical disease and improving risk stratification. To review the available evidence on the role of ctDNA in MIBC, particularly after radical cystectomy, as a marker of MRD and a tool to guide clinical decision-making. A structured narrative review of 37 studies published between 1999 and 2025 was conducted, including prospective and retrospective cohorts, as well as clinical trials. Studies evaluating ctDNA in the perioperative setting and reporting clinically relevant outcomes such as survival and recurrence were analyzed. Preoperative ctDNA detection is associated with higher tumor burden and worse prognosis. However, its greatest clinical value is observed in the postcystectomy setting, where ctDNA positivity identifies MRD and predicts recurrence months before radiological detection. Longitudinal ctDNA dynamics enhance predictive accuracy, with persistence or conversion to positivity indicating high relapse risk. Tumor-informed platforms show higher sensitivity, whereas tumor-agnostic approaches offer greater accessibility. Recent evidence suggests ctDNA may guide adjuvant treatment decisions. Postcystectomy ctDNA is a robust biomarker of MRD with significant prognostic value and potential clinical utility. Its integration may enable personalized management of MIBC, although standardization and further prospective validation are required before routine implementation.