TOPLINE:

Circulating tumour DNA (ctDNA) monitoring identified patients with muscle-invasive bladder cancer who showed significantly longer disease-free survival and overall survival when treated with adjuvant atezolizumab vs placebo.

METHODOLOGY:

• Researchers conducted a phase 3, international, double-blind, randomised trial at 157 sites across 24 countries and enrolled 761 adult patients at risk for recurrence after cystectomy between May 2021 and November 2024.
• Serial ctDNA monitoring was performed every 6 weeks for 9 months, with a final test at 1 year post-cystectomy, using the Signatera molecular residual disease test outside mainland China and a test from Tianjin Medical Laboratory, BGI in mainland China.
• Patients who tested positive for ctDNA (n = 250) were randomly assigned in a 2:1 ratio to receive either intravenous atezolizumab (dosage, 1680 mg; n = 167) or placebo (n = 83) every 4 weeks for 12 cycles, up to 1 year, or until disease recurrence or the occurrence of unacceptable toxic effects, whichever occurred first.
• Patients who persistently tested negative for ctDNA (n = 357) did not receive either atezolizumab or placebo during the study.
• The primary endpoint was disease-free survival, with overall survival being a key secondary endpoint; patients with persistent ctDNA-negative status were monitored for disease-free survival outcomes.

TAKEAWAY:

• The median disease-free survival was higher with atezolizumab than with placebo (9.9 vs 4.8 months; stratified hazard ratio [HR] for the first event of disease recurrence or death, 0.64; P = .005) in patients with ctDNA-positive status at a median follow-up of 16.1 months.
• The median overall survival was significantly longer with atezolizumab than with placebo (32.8 vs 21.1 months; stratified HR for death, 0.59; P = .01).
• Among patients with persistent ctDNA-negative status, disease-free survival was 95% after 1 year and 88% after 2 years.
• Adverse events of grade 3 or 4 occurred in 28% of patients who received atezolizumab vs 22% of those who received placebo, with treatment-related adverse events noted in 7% vs 4%.

IN PRACTICE:

"In this trial involving patients with muscle-invasive bladder cancer, ctDNA-guided adjuvant therapy with atezolizumab led to significantly longer disease-free survival and overall survival than placebo," the authors wrote. "These findings support the clinical usefulness of ctDNA-based testing for molecular residual disease in guiding adjuvant treatment decisions for bladder cancer and may have implications for other solid tumors with heterogeneous outcomes after curative-intent surgery," they added.

SOURCE:

This study was led by Thomas Powles, MD, Barts Cancer Institute, Queen Mary University of London, London, England. It was published online on October 20, 2025, in The New England Journal of Medicine.

LIMITATIONS:

The interpretation of some subgroup analyses was limited by small sample sizes and broad CIs. The median follow-up duration for survival was relatively short. The trial was initiated before the widespread availability of enfortumab vedotin with pembrolizumab for the treatment of advanced disease. Patients from North America and Black patients were underrepresented in this trial.

DISCLOSURES:

This study was funded by F. Hoffmann-La Roche. Several authors reported receiving grants and consulting fees and having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.