Bladder Cancer with Undetectable Circulating Tumor DNA After Radical Cystectomy May Be Amenable to a Less Intense Imaging Surveillance Protocol: A Diagnostic Accuracy Study.

Background and objective: Circulating tumor DNA (ctDNA) has shown promise as a prognostic biomarker for bladder cancer management. Current surveillance guidelines for patients with muscle-invasive bladder cancer recommend intense postoperative surveillance. Our aim was to assess the diagnostic performance of ctDNA in comparison to imaging studies for detection of disease recurrence after radical cystectomy.

Methods: We analyzed patients who underwent robot-assisted radical cystectomy and prospective tumor-informed ctDNA analysis (Signatera™) between 2021 and 2023 at a single institution. Patients with postoperative imaging and ctDNA results were included; patients with nonurothelial histology or missing ctDNA data were excluded. Diagnostic accuracy was evaluated at the patient level using imaging findings as the reference standard and ctDNA as the index test. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ctDNA measurement were calculated.

Key findings and limitations: A total of 94 patients were included (median age 70 yr, interquartile range [IQR] 63-77). Most had ≥pT2 disease (75.4%) that was node-negative disease (71.3%). Over median follow-up of 16 mo (IQR 9-22), 388 imaging studies and 283 ctDNA tests were performed. ctDNA demonstrated sensitivity and an NPV of 100.0% (95% confidence interval [CI] 100.0-100.0%), specificity of 91.8% (95% CI 87.6-95.5%), and a PPV of 84.5% (95% CI 76.8-91.3%).

Conclusions and clinical implications: ctDNA measurement may serve as a valuable tool for bladder cancer surveillance after cystectomy. Patients with persistently undetectable ctDNA may benefit from less intensive surveillance protocols aligned with their lower risk of recurrence. This strategy warrants further research to validate its clinical utility and support integration into routine practice.