Trimodality therapy (TMT) is a bladder-sparing treatment approach for patients with muscle-invasive bladder cancer (MIBC). Although plasma circulating tumor DNA (ctDNA) is correlated with treatment response and outcomes following cystectomy for MIBC, the association of plasma ctDNA with clinical outcomes in patients treated with TMT is poorly characterized.
Patients with MIBC who received TMT at Dana-Farber/Brigham and Women's Cancer Center or Massachusetts General Hospital were consented to a research protocol and underwent ctDNA evaluation at baseline and at regular intervals following TMT using the commercially available SignateraTM assay. All patients also underwent routine post-TMT surveillance including cross-sectional imaging and cystoscopic evaluation. The association between ctDNA status and clinical disease status was assessed.
Eighty-four patients had at least one ctDNA result. Fifty-nine patients had a ctDNA test performed prior to chemoradiotherapy (CRT) and 19 (32%) had detectable ctDNA. Forty-six patients had paired pre- and post-CRT ctDNA results available: nearly all (29/31, 94%) patients with undetectable ctDNA prior to CRT also had undetectable ctDNA at the first post-CRT assessment whereas 11 of 15 patients (73%) with detectable ctDNA prior to CRT converted to undetectable ctDNA following CRT. Sixten patients (19%) developed metastatic disease, and detectable ctDNA following CRT was strongly correlated with metastatic recurrence (p<0.0001). Conversely, no patients with an isolated muscle-invasive (n=5) or non-muscle-invasive (n=7) bladder recurrence had a post-TMT test demonstrating detectable ctDNA prior to recurrence.
ctDNA detectability is strongly correlated with metastatic but not local disease recurrence in patient with MIBC following TMT.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2026 Jan 26 [Epub ahead of print]
Ilana B Epstein, Adetolani Odogiyon, Stephanie Berg, Yukako Otani, Charlene Mantia, Isabella R Pompa, Matthew Mossanen, Joshua Wan, Anurag Saraf, Mark Preston, Arvind Ravi, Filipe Carvalho, Cameron Herberts, Adam ElNaggar, Timothy Clinton, Daniel Roberts, Luke Peng, Bradley McGregor, Joaquim Bellmunt, Sophia C Kamran, Jacob E Berchuck, Jason A Efstathiou, David T Miyamoto, Kent W Mouw
Dana-Farber Cancer Institute Boston United States., Massachusetts General Hospital United States., Dana-Farber Cancer Institute Boston, MA United States., Massachusetts General Hospital Boston, MA United States., Dana-Farber Cancer Institute Boston, Massachusetts United States., Brigham and Women's Hospital United States., Brigham and Women's Hospital Boston, MA United States., Dana-Farber Cancer Institute United States., Natera (United States) San Carlos, California United States., Natera (United States) San Carlos, CA United States., Emory University Atlanta, Georgia United States., Massachusetts General Hospital Charlestown, MA United States.