Circulating tumor DNA as a tool for precision management in bladder cancer: A narrative review

Abstract

Circulating tumor DNA (ctDNA) has emerged as a potential paradigm-shifting biomarker for precision management of bladder cancer, particularly muscle-invasive bladder cancer (MIBC). Although ctDNA assays are not yet widely implemented in routine clinical practice, a growing body of evidence supports its utility in diagnosis, risk stratification, prognosis, therapeutic decision-making and post-treatment surveillance. This review summarizes the current and evolving roles of ctDNA in bladder cancer management, with particular emphasis on completed and ongoing clinical trials that are shaping its integration into standard care. A comprehensive literature search was conducted across PubMed, MEDLINE, Google Scholar, Embase, and Scopus for studies published between January 2005 and November 2025. The search strategy included the following terms: bladder cancer, circulating tumor DNA, liquid biopsy, circulating biomarkers. A total of 172 English-language records were initially identified. After screening for relevance to the objectives of this review, 29 studies met the inclusion criteria and were analyzed in detail. In bladder cancer, ctDNA has demonstrated prognostic value across multiple disease stages, including diagnosis, assessment of response to neoadjuvant chemotherapy, and surveillance post-cystectomy. In the adjuvant setting, ctDNA-positivity has been associated with improved outcomes when patients are subsequently treated with immune checkpoint inhibitors, as shown in the IMvigor010 trial and further explored in the ongoing IMvigor011 trial. Ongoing studies (e.g. MODERN and TOMBOLA) aim to further validate ctDNA-guided treatment strategies, and their role in prognostication and disease monitoring. Multiple studies and ongoing trials have established the utility of ctDNA in the realm of bladder cancer with indications spanning detection of recurrence, guiding use of adjuvant therapy, and prognosis evaluation. Despite this momentum, several barriers continue to limit broader clinical integration, including high testing costs, absence of standardized assay protocols, and significant inter-laboratory variability. Addressing these challenges through robust clinical trials and standardized regulatory frameworks will be essential for the widespread and reliable adoption of ctDNA in bladder cancer care.