Circulating Tumor DNA in Muscle-Invasive Bladder Cancer: Implications for Prognosis and Treatment Personalization

Muscle-invasive bladder cancer (MIBC) is a biologically aggressive disease with high recurrence rates, despite advances in surgical and systemic therapies. Circulating tumor DNA (ctDNA), a tumor-specific fraction of cell-free DNA, has emerged as a promising non-invasive biomarker for the real-time assessment of tumor burden, treatment response, and minimal residual disease (MRD). This review explores the biological basis, detection technologies, and clinical utility of ctDNA in MIBC, highlighting its role in preoperative risk stratification, postoperative surveillance, and personalized decision-making for adjuvant and systemic therapies. We critically examine current evidence from pivotal trials and ongoing studies that support ctDNA's prognostic and predictive value. Additionally, we discuss emerging applications, including ctDNA-guided immunotherapy, integration with imaging and molecular data, and potential to inform bladder-sparing strategies. While ctDNA presents technical and logistical challenges, its incorporation into prospective clinical workflows promises to enhance precision oncology and improve outcomes in patients with MIBC.