Clinical trialPhase 3Bladder cancer

ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer

N Engl J Med · 2025761 patients enrolled; 250 ctDNA-positive patients were randomised (167 atezolizumab, 83 placebo)

Powles T, Kann AG, Castellano D, et al. N Engl J Med. 2025. 393:2395-2408

Study type: Clinical trial
Study name: IMvigor011
Phase: Phase 3
Design: Randomised, double-blind, placebo-controlled trial (2:1 randomisation) in patients who became ctDNA-positive during serial monitoring
Sample size: 761 patients enrolled; 250 ctDNA-positive patients were randomised (167 atezolizumab, 83 placebo)
Source: N Engl J Med · 2025
Trial registration: NCT04660344

In plain words

After the bladder has been removed because of invasive cancer, not every patient needs extra treatment. In this study, patients were monitored for up to one year with a blood test called ctDNA. Those in whom traces of tumour DNA were found in the blood and who received the immunotherapy drug atezolizumab stayed free of disease for longer and also lived longer. Patients whose test stayed negative every time did very well without any treatment and were spared its side effects.

Key results

9.9 vs 4.8 months

Median disease-free survival

HR 0.64 (95% CI 0.47–0.87); P = 0.005

32.8 vs 21.1 months

Median overall survival

HR 0.59 (95% CI 0.39–0.90); P = 0.01

95% at 1 year and 88% at 2 years

DFS in persistently ctDNA-negative patients (357 patients)

No adjuvant treatment

Drugs in this study:Atezolizumab (Tecentriq)

Dose and schedule cards

ctDNA-guided adjuvant atezolizumab (IMvigor011)

MIBC after cystectomy with positive ctDNA (molecular residual disease) on serial testing 6 weeks to 1 year after surgery, using an FDA-authorized test; in the trial, ypT2 to T4a/ypN+ after neoadjuvant therapy or pT2 to T4a/pN+ without itCycle length: 14, 21 or 28 daysOn the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Drug	Dose	Route	Schedule
Atezolizumab	840 mg every 2 weeks, 1200 mg every 3 weeks or 1680 mg every 4 weeks	IV; first infusion over 60 minutes, subsequent infusions over 30 minutes if tolerated	According to the selected dose (trial: 1680 mg on Day 1 every 28 days)

Cycle length: 14, 21 or 28 days
Duration: Up to 1 year (trial: 12 cycles)

Per the FDA label and the IMvigor011 trial.

On the page “Bladder cancer” · Muscle-invasive cancer (MIBC): after cystectomy (adjuvant)

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Atezolizumab

Atezolizumab 1680 mg IV on day 1 of each 28-day cycle (every 4 weeks), for 12 cycles or up to 1 year, or until recurrence, unacceptable toxicity or withdrawal.

2Placebo

IV placebo on day 1 of each 28-day cycle (every 4 weeks) for up to 1 year.

3Surveillance (persistently ctDNA-negative)

Patients who remained ctDNA-negative up to 12 months after cystectomy received no treatment and were followed up.

Source of the regimen details: ClinicalTrials.gov NCT04660344 (atezolizumab 1680 mg IV every 4 weeks for up to 12 cycles or 1 year)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with muscle-invasive bladder cancer after cystectomy with no radiological evidence of disease, monitored for up to 1 year with serial ctDNA testing (Signatera); patients who became ctDNA-positive were randomised.

Endpoints

Primary endpoint: investigator-assessed disease-free survival (DFS).

Key secondary endpoint: overall survival (OS), with hierarchical testing.

Safety and side effects

Grade 3 or 4 adverse events: 28% with atezolizumab versus 22% with placebo (treatment-related 7% versus 4%). Fatal adverse events: 3% versus 2% (treatment-related 2% versus none).

Clinical significance and place in guidelines

In May 2026 the FDA approved atezolizumab (Tecentriq and Tecentriq Hybreza) as adjuvant treatment for adults with muscle-invasive bladder cancer with ctDNA-based molecular residual disease after radical cystectomy, and accepted the Signatera CDx test as the companion diagnostic. This is the first approval of a ctDNA-guided adjuvant therapy in bladder cancer.

Limitations

Not all ctDNA-positive patients were randomised (only eligible ones); funded by the manufacturer; the ctDNA test used (Signatera) requires tumour tissue; there was no direct comparison with adjuvant nivolumab (the standard treatment, which does not require ctDNA).

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.