Real-World Experience with a Commercial Circulating Tumor DNA Assay in Non–muscle-invasive Bladder Cancer

Circulating tumor DNA (ctDNA) is an emerging biomarker in advanced bladder cancer, but its role in non-muscle-invasive bladder cancer (NMIBC) remains undefined. We conducted a retrospective study of 23 patients with NMIBC who underwent serial ctDNA monitoring using the commercially available Signatera assay at a single institution. ctDNA was detected in 35% of patients, with two illustrative cases highlighting its clinical utility. In one case, baseline ctDNA positivity prompted earlier reimaging that revealed locally advanced disease, leading to initiation of systemic therapy followed by planned consolidative cystectomy. In another case, ctDNA positivity following salvage intravesical therapy detected early recurrence, prompting a shift from maintenance intravesical therapy to radical cystectomy. These findings suggest that ctDNA may facilitate early detection of molecular residual disease and guide treatment decisions in NMIBC, particularly in patients with bacillus Calmette-Guérin-unresponsive disease. Prospective studies are needed to validate the role of ctDNA in risk stratification and treatment optimization for this high-risk population.