Circulating tumor DNA (ctDNA) status after radical cystectomy may be able to effectively guide adjuvant treatment decisions for patients with muscle-invasive bladder cancer, according to data presented at the 26th Annual Meeting of the Society of Urologic Oncology (SUO).¹

Results of an exploratory subgroup analysis of the phase III IMvigor011 trial showed that adjuvant atezolizumab provided significant benefit to ctDNA-positive patients while sparing ctDNA-negative patients from potentially unnecessary treatment, regardless of conventional pathologic staging.

These findings demonstrate the utility of a biomarker-driven approach to enhance risk determination beyond traditional surgical staging, representing a crucial step towards personalized medicine in muscle-invasive bladder cancer, study authors reported.

“The beauty of this study is that it’s the first biomarker-driven study in muscle-invasive bladder cancer,” stated Jürgen E. Gschwend, MD, PhD, Distinguished Professor and Chairman of Urology at the Technical University of Munich, Germany, who presented the findings. “There is a strong need to differentiate patients at risk of recurrence from those who are not, and ctDNA detection of measurable residual disease (MRD) is highly prognostic postcystectomy.”

As Dr. Gschwend explained, focusing adjuvant treatment on ctDNA-positive patients potentially enriches the benefit of patients following radical cystectomy while sparing ctDNA-negative patients from unnecessary treatment and its associated toxicities.

The global, randomized phase III IMvigor011 trial had previously shown that serial ctDNA monitoring could identify patients with muscle-invasive bladder cancer who benefit from adjuvant atezolizumab vs placebo, while sparing patients who persistently tested ctDNA-negative from unnecessary treatment. This exploratory analysis further aimed to characterize the relationship between pathologic staging at cystectomy, ctDNA status, and clinical outcomes.

IMvigor011 Study Design

The IMvigor011 study included adult patients with muscle-invasive bladder cancer ranging from locally confined (T2) to locally advanced (T4a), with or without regional lymph node involvement (N0–N1), and no distant metastases (M0). This included patients who had undergone radical cystectomy, recognizing that some may have achieved a pathologic complete response (yT0, meaning no residual invasive tumor in the surgical specimen after neoadjuvant therapy) following neoadjuvant therapy prior to surgery.

After radical cystectomy, patients underwent serial ctDNA testing every 6 weeks and received quarterly imaging. Patients who were ctDNA-positive or converted from negative to positive and were radiologically negative were randomly assigned 1:1 to receive open-label atezolizumab (1,680 mg intravenously every 4 weeks) or placebo for up to 1 year. Patients who were persistently ctDNA-negative at any time point received no adjuvant treatment and underwent surveillance.

The initial presentation of data from IMvigor011 showed a clear and significant impact in favor of atezolizumab vs placebo for both disease-free survival and overall survival in the ctDNA-positive population.

This exploratory analysis included 761 patients who were enrolled in surveillance, with 379 patients testing ctDNA-positive at any time and 377 persistently testing ctDNA-negative. The ctDNA positivity rate strongly correlated with pathologic staging at cystectomy. For instance, ctDNA positivity increased from 20.5% in pT2N0 patients (meaning pathologic stage T2, no lymph node involvement, based on surgical specimen, likely without prior neoadjuvant therapy) to 82.5% in (y)pT3–4N+ patients (meaning pathologic stage T3 or T4a, with lymph node involvement, in patients who may have received neoadjuvant therapy). However, even in organ-confined pT2N0 or yT2N0 patients, ctDNA positivity rates were 20% and 33%, respectively, demonstrating that surgical staging alone is insufficient to predict ctDNA status accurately.

ctDNA Status Predicts Benefit and Guides De-escalation

As Dr. Gschwend reported, in patients who tested ctDNA-positive and were randomly assigned, adjuvant atezolizumab provided consistent benefit regardless of conventional risk factors. The benefit of atezolizumab was observed across all subgroups, said Dr. Gschwend, including different tumor stages (y)pT2 [pathologic stage T2, with or without prior neoadjuvant therapy] vs (y)pT3-4 [pathologic stage T3 or T4a, with or without prior neoadjuvant therapy]), nodal status (y)pN0 [pathologic N0] vs (y)pN+ [pathologic N+]), and prior neoadjuvant chemotherapy (no prior neoadjuvant chemotherapy vs prior neoadjuvant chemotherapy).

In ctDNA-positive (y)pT2 patients, atezolizumab showed a disease-free survival median of 14.8 months vs 8.1 months with placebo (unstratified hazard ratio [HR] = 0.66). In (y)pT3–4 patients, it was 8.3 months vs 6.3 months (unstratified HR = 0.84). The overall survival benefit was similarly observed across these subgroups.

Conversely, patients who persistently tested ctDNA-negative had a uniformly low risk of recurrence or death, regardless of their tumor stage, nodal status, or prior neoadjuvant chemotherapy. For these ctDNA-negative patients, 24-month overall survival rates were consistently high, exceeding 95% across all subgroups, including those with higher tumor stages or nodal involvement that would conventionally be considered high-risk.

“These findings show that ctDNA positivity rates were higher in patients with high tumor stage or positive nodal status, but surgical staging alone was insufficient to predict ctDNA status,” said Dr. Gschwend, who emphasized that adjuvant atezolizumab provided benefit to ctDNA-positive patients regardless of their baseline clinical characteristics. “Crucially, patients who persistently tested ctDNA-negative had an excellent prognosis with a uniformly low risk of recurrence or death, making them candidates for de-escalated therapy.”

According to Dr. Gschwend, these results strongly support the use of serial ctDNA testing after radical cystectomy to enhance risk determination beyond classical surgical pathologic staging.

“This approach can effectively identify patients with ctDNA-positive status who truly benefit from adjuvant atezolizumab, while simultaneously sparing patients who persistently test ctDNA-negative from unnecessary treatments and their associated toxicities, thereby optimizing personalized care in [muscle-invasive bladder cancer],” Dr. Gschwend concluded.

Disclosure: Dr. Gschwend reported financial interests with Roche.

Reference

1.Gschwend GE, Bellmunt J, Arslan C, et al. Circulating tumor DNA-guided adjuvant atezolizumab vs placebo in patients with muscle-invasive bladder cancer after radical cystectomy: Exploratory subgroup analysis of the phase 3 IMvigor011 trial. 26th Annual Meeting of the Society of Urologic Oncology. Presented on December 5, 2025.