Sustained ctDNA Negativity Confers Optimal Outcomes in MIBC

In a conversation with CancerNetwork^® at the 2026 ASCO Genitourinary Cancers Symposium, Joaquim Bellmunt, MD, PhD, discussed the background and key findings from an exploratory analysis of the phase 3 IMvigor011 trial (NCT04660344) examining how ctDNA affects efficacy outcomes in patients with muscle-invasive bladder cancer (MIBC).

Initially, he explained that the IMvigor011 trial assessed atezolizumab (Tecentriq) vs placebo among patients with ctDNA-positive disease. Furthermore, he highlighted that across a 1-year examination period, patients who began with ctDNA negativity could have been randomly assigned to treatment with the investigational agent or placebo.

One key finding Bellmunt highlighted was that patients who experienced a recurrence of their disease within 6 months of the study period typically had a high concentration of ctDNA. In contrast, late recurrences that were observed in the latter 6 months were mostly observed in patients with low concentrations of ctDNA. Finally, he expressed that later recurrence was associated with the most optimal outcomes, with patients maintaining negative ctDNA status throughout the duration of study experiencing the best outcomes.

Bellmunt is the director of the Bladder Cancer Center at Dana-Farber Cancer Institute and a professor of Medicine at Harvard Medical School.

Transcript:

We did an exploratory analysis of the ctDNA in the patients who were included in the IMvigor011 [trial]…. IMvigor011 is a trial that explored the use of ctDNA to drive the indication to administer adjuvant atezolizumab in patients with [MIBC] after surgery who have risk factors for recurrence. This trial randomly [assigned] patients to receive atezolizumab or placebo if they were ctDNA positive. If they were ctDNA negative, the patients were followed.

Another important thing is that the patients who were [treated with atezolizumab] in the trial, if the ctDNA was positive at baseline, were followed throughout a year. If at any point the ctDNA-negative [status] became positive, they were allowed to be included in the trial and be randomly [assigned]. Meaning, we have 2 populations of patients: patients who have early ctDNA positivity, and patients who develop later positivity of ctDNA.

What we have been doing is an analysis to understand the natural history of the ctDNA and how this is impacting prognosis. We plot the concentration of ctDNA with the timing, and what we see is that, initially, [for] the majority of patients who recur––and recurrence is based on ctDNA––it happens in the first 6 months, and the concentration is high. [For] patients who recur later, after [the next] 6 months, the concentration of ctDNA is usually low. Then, we have translated these findings to see how they are impacting outcomes.

[What] we see in the outcomes, correlating with the disease-free survival [DFS] and overall survival, is patients who recur early… are doing worse, meaning the DFS is shorter. If they are recurring later, they have much better outcomes. However, at any time point, they are going to recur, meaning that the patients [with the best outcomes] are the ones who maintain the ctDNA negativity completely throughout all of the study.

Reference

Powles T, Grindheim J, Yilmaz M, et al. Circulating tumor (ct)DNA-guided adjuvant atezolizumab (atezo) in muscle-invasive bladder cancer (MIBC): exploratory analysis of ctDNA dynamics in the IMvigor011 trial. J Clin Oncol. 2026;44(suppl 7):633. doi:10.1200/JCO.2026.44.7_suppl.633