Patients with muscle-invasive bladder cancer who tested positive for circulating tumor DNA (ctDNA) after cystectomy may benefit from immunotherapy with the PD-L1 inhibitor atezolizumab compared to placebo, whereas ctDNA-negative patients may potentially be spared unnecessary treatment. These findings are based on results from the global, randomized, phase III IMvigor011 trial co-led by investigators from Dana-Farber Cancer Institute, the Technical University of Munich, and Queen Mary University of London.
The results of the IMvigor011 trial were presented in a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress 2025 (Abstract LBA8) and published simultaneously by Powles et al in The New England Journal of Medicine.
Patients with positive ctDNA taking atezolizumab had a 36% lower risk of disease recurrence than those taking placebo, regardless of whether they were ctDNA-positive immediately after surgery or if ctDNA positivity emerged during screening up to a year after surgery. Risk of death was also reduced by 41%.
“By selecting patients based on ctDNA, we see a benefit not only for disease-free survival but also for overall survival with atezolizumab,” said co-principal investigator Joaquim Bellmunt, MD, PhD, Director of the Bladder Cancer Center at Dana-Farber Cancer Institute. “This is the first time that an adjuvant immunotherapy trial has shown a benefit for survival in selected patients based on ctDNA testing.”
Joaquim Bellmunt, MD, PhD
IMvigor 010
An earlier trial, IMvigor010—led by Dr. Bellmunt—tested the use of atezolizumab in patients with muscle-invasive bladder cancer after surgery.
The study did not show a benefit across all patients, but a retrospective data analysis suggested that patients with positive ctDNA did benefit from treatment. A positive ctDNA test indicates the presence of measurable residual disease (MRD).
The IMvigor011 study was designed to test the hypothesis that ctDNA could be used to guide the use of immunotherapy with atezolizumab in patients with MRD.
IMvigor011 Design and Key Findings
In the trial, 800 patients who had no clinical evidence of cancer after surgery were screened using a personalized blood test (ctDNA) every 6 weeks for 9 months and up to 1 year. Of these, 250 ctDNA-positive patients were randomly assigned in a 2:1 ratio to receive either atezolizumab or placebo.
Patients who remained ctDNA-negative received no additional treatment. Of those patients, 89% remained disease-free and more than 90% were still living at a median follow up of 21.8 months.
“What these findings tell us is that this ctDNA test is detecting MRD and can identify patients who still have bladder cancer after surgery and might benefit from receiving atezolizumab,” said Dr. Bellmunt. “Further, it suggests that patients who are persistently ctDNA-negative have a low risk of recurrence and can be spared from unnecessary treatment.”
No new side effects were identified. Based on these data, regulatory agencies will determine if standard therapy should change to link the use of atezolizumab with a ctDNA test in patients with this indication.
Disclosure: This study was funded by F. Hoffmann-La Roche Ltd, with Natera as a collaborator. For full disclosures of the study authors, visit nejm.org.
