Molecular Monitoring Approach Helps Bladder Cancer Patients Avoid Surgery

Muscle-invasive bladder cancer is typically treated with chemotherapy followed by radical cystectomy, the complete removal of the bladder. While often effective, the surgery significantly affects quality of life and requires permanent urinary diversion. Now, new research suggests that ultra-sensitive tumor DNA testing in blood and urine may help identify patients who can safely preserve their bladder without compromising cancer outcomes.

Researchers at the Icahn School of Medicine at Mount Sinai (New York, NY, USA) evaluated circulating tumor DNA (ctDNA) in blood and urine tumor DNA (utDNA) in urine from patients enrolled in a clinical trial testing a bladder-sparing strategy. The molecular assays were developed in collaboration with investigators at Johns Hopkins University (Baltimore, MD, USA). The approach aimed to detect minimal residual disease that may not be visible on imaging or biopsy.

Among patients who achieved a complete clinical response after systemic therapy, three-year bladder-intact survival reached 69%, supporting the durability of bladder preservation in selected individuals. Detectable ctDNA before systemic therapy was strongly associated with higher metastatic risk. In contrast, only 4.5% of patients with undetectable baseline ctDNA developed metastases. Patients with undetectable ctDNA either before or after treatment had an exceptionally low risk of metastatic recurrence.

Urine tumor DNA provided complementary insights. utDNA was more sensitive than blood-based ctDNA for detecting residual disease confined to the bladder. Detectable utDNA in patients without visible disease was associated with shorter bladder-intact survival. The findings, published in the Proceedings of the National Academy of Sciences, suggest that combined blood and urine DNA testing could help guide personalized treatment decisions, identifying patients who may safely avoid radical cystectomy.

More precise assessment of residual disease may reduce overtreatment while maintaining strong cancer control. According to the researchers, these results provide a scientific foundation for incorporating ctDNA and utDNA monitoring into clinical decision-making. However, ongoing studies are underway to validate the approach in additional patient cohorts.

“These findings show that blood and urine DNA testing provide complementary information. Together, they offer a powerful new way to identify patients most likely to benefit from bladder preservation,” said Professor Matthew D. Galsky, MD, first author of the study. “This research represents an important step toward personalized care in muscle-invasive bladder cancer. As therapies and diagnostics improve, we must ensure we are not overtreating patients who may already be cured.”

Related Links:
Icahn School of Medicine at Mount Sinai
Johns Hopkins University