Urothelial bladder cancer (UBC) carries significant mortality and treatment morbidity. Conventional diagnostic and monitoring methods, including cystoscopy and biopsy, are invasive and limited in sensitivity. Circulating tumor DNA (ctDNA), a minimally-invasive "liquid biopsy," has emerged as a promising tool for real-time disease assessment. This study aimed to systematically evaluate the diagnostic, prognostic, and predictive value of plasma and urine ctDNA in localized, locally advanced, and metastatic UBC.
A systematic review was conducted according to PRISMA guidelines using PubMed, MEDLINE, and Web of Science databases (January 2016-October 2025). Eligible studies evaluated plasma and urine ctDNA. Main outcomes included diagnostic performance, correlation with tissue mutations, disease monitoring, and prognostic or predictive value. Data synthesis focused on ctDNA detection methods, timing relative to treatment, and survival outcomes. KEY FINDINGS AND LIMITATIONS: ctDNA showed strong concordance with tumor tissue mutations and high potential for real-time monitoring of tumor burden. Data are more robust in muscle-invasive bladder cancer (MIBC) than non-muscle-invasive bladder cancer (NMIBC). Postcystectomy ctDNA positivity was an independent predictor of recurrence-free, progression-free, and overall survival. ctDNA clearance correlated with response to neoadjuvant chemotherapy and immune checkpoint inhibitors. In metastatic disease, high ctDNA mutation burden was associated with shorter overall survival and resistance mechanisms, such as PIK3CA-mediated fibroblast growth factor receptor inhibitor resistance. Limitations included heterogeneous methodologies, variable assay sensitivity, and small patient cohorts.
ctDNA represents a powerful non-invasive biomarker for diagnosis, surveillance, and treatment guidance in UBC. Ongoing phase III trials (IMvigor011, TOMBOLA, MODERN) may establish its clinical utility as a standard tool for personalized disease management.
European urology oncology. 2026 Mar 19 [Epub ahead of print]
Igor Duquesne, Isabelle Epelbaum, Doriane Prost, Mathilde Haberstich, Caio Vinícius Suartz, Hélène Blons, Valérie Taly, Pierre Laurent-Puig, Amir Horowitz, John P Sfakianos, Constance Thibault, François Audenet
Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Urology, Henri Mondor University Hospital, Assistance Publique-Hopitaux de Paris, Créteil, France; Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP, Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France., Department of Immunology and Immunotherapy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP, Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France; Department of Urology, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France., Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP, Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France; Department of Medical Oncology, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France., Department of Urology, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France., Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP, Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France., Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Centre de Recherche des Cordeliers, Sorbonne Université, Inserm, Université Paris Cité, Personalized Medicine, Phamacogenomics and Therapeutic Optimization, Paris, France; Institut du Cancer Paris CARPEM, APHP, Centre, Department of Biology, Hôpital Européen Georges Pompidou, Paris, France; Department of Urology, Hôpital Européen Georges Pompidou, Assistance Publique-Hopitaux de Paris, Paris, France. Electronic address: .