Blood Test Predicts Which Bladder Cancer Patients May Safely Skip Surgery

Muscle-invasive bladder cancer (MIBC) often requires removal of the bladder, a procedure that significantly affects quality of life and carries a risk of complications. While newer treatments have improved outcomes, clinicians still lack reliable tools to determine which patients can safely avoid surgery. Detecting metastatic risk early is critical, but identifying local recurrence within the bladder remains challenging. Now, new research findings show that circulating tumor DNA (ctDNA) testing can predict metastatic risk in patients undergoing bladder-sparing treatment, helping guide more personalized treatment decisions.

In a study by Fox Chase Cancer Center (Philadelphia, PA, USA) that reported updated data from the phase 2 RETAIN-2 clinical trial, researchers evaluated a response-adapted bladder-preservation strategy using neoadjuvant chemotherapy combined with immunotherapy before deciding whether surgery was necessary. More than 70 patients with MIBC received combination chemotherapy plus nivolumab. Patients who achieved a complete response entered active surveillance instead of undergoing immediate cystectomy. Blood samples were analyzed at multiple timepoints to measure ctDNA, which consists of small DNA fragments shed by dying cancer cells during treatment.

The absence of ctDNA after treatment was associated with favorable outcomes, regardless of whether patients kept their bladder or underwent removal. Patients who were ctDNA-positive after treatment were significantly more likely to develop metastatic disease. Overall, 80% of patients who entered surveillance remained metastasis-free after two years. However, ctDNA did not effectively detect local recurrence within the bladder. Among 22 patients who developed recurrence in the bladder, 19 did not show increased ctDNA levels. The updated findings from RETAIN-2 indicate that while ctDNA predicts metastatic risk, additional tools are needed to monitor local disease.

The results, published in Journal of Clinical Oncology, suggest that ctDNA testing could help identify patients most likely to benefit from bladder-sparing treatment while still detecting those at higher risk for metastasis. By incorporating ctDNA into clinical decision-making, physicians may better determine who can safely avoid surgery and who requires more aggressive intervention. Researchers plan to follow RETAIN-2 participants for five years to assess long-term outcomes. The upcoming RETAIN-3 trial will further explore the use of ctDNA as a predictive biomarker to refine treatment strategies.

“This tells us ctDNA can be incorporated into the decision-making of who should keep their bladder and who should not, knowing that we also need additional tests or biomarkers to detect local recurrence early in patients who undergo active surveillance,” said Associate Professor Pooja Ghatalia, MD, first author of the study.

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Fox Chase Cancer Center