ctDNA Clearance Linked to Improved Metastasis-Free Survival in Bladder Cancer

Findings from the RETAIN trials suggest ctDNA monitoring can help guide bladder-sparing treatment approaches for muscle-invasive bladder cancer.

Published on Feb. 28, 2026

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An integrated analysis of the RETAIN-1 and RETAIN-2 trials found that post-treatment ctDNA negativity or clearance correlated with improved metastasis-free survival among patients with muscle-invasive bladder cancer (MIBC). Those with undetectable ctDNA following treatment experienced a lower risk of systemic recurrence, suggesting ctDNA monitoring can help refine patient selection for bladder-sparing approaches.

Why it matters

The findings highlight the potential of incorporating ctDNA analysis into the decision-making process for MIBC patients, helping identify those who can safely avoid radical cystectomy and maintain an intact bladder. This is particularly significant as radical cystectomy is a life-altering procedure with significant morbidity.

The details

The RETAIN trials evaluated a bladder-sparing approach combining neoadjuvant accelerated MVAC chemotherapy with the checkpoint inhibitor nivolumab, followed by comprehensive restaging and active surveillance for select patients. The analysis found that 68% of patients on active surveillance remained metastasis-free while maintaining an intact bladder. Importantly, ctDNA positivity was associated with a 10.7 times higher risk of inferior metastasis-free survival, underscoring its prognostic value for systemic disease control.

  • The RETAIN-2 trial met its primary endpoint, demonstrating a 70% metastasis-free survival rate at 2 years within the intention-to-treat population.
  • Among the cohort that moved into active surveillance, the 2-year metastasis-free survival was even higher at 85%.

The players

Pooja Ghatalia, MD

Associate professor, Department of Hematology/Oncology, at Fox Chase Cancer Center in Philadelphia, Pennsylvania, and the presenter of the findings.

RETAIN-1

A single-arm phase 2 trial focused on patients with clinical T2 to T4a, N0, M0 muscle-invasive bladder cancer.

RETAIN-2

A clinical trial that met its primary endpoint by demonstrating a 70% metastasis-free survival rate at 2 years within the intention-to-treat population.

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What they’re saying

“Incorporating ctDNA into the decision-making process helps refine who can safely keep their bladder.”

— Pooja Ghatalia, MD, Associate professor, Department of Hematology/Oncology, at Fox Chase Cancer Center (cancernetwork.com)

What’s next

The study suggests that for patients who remain ctDNA-negative but show clinical evidence of local disease, bladder-directed therapies such as chemoradiation or intravesical Bacillus Calmette-Guérin remain viable options.

The takeaway

The findings from the RETAIN trials demonstrate the potential of using ctDNA analysis to guide bladder-sparing treatment approaches for MIBC patients, helping identify those who can safely avoid radical cystectomy and maintain an intact bladder while still effectively managing their disease.