New Molecular Testing May Help Bladder Cancer Patients Avoid Surgery

Ultrasensitive testing of tumor-derived DNA in blood and urine may help identify patients with muscle-invasive bladder cancer who can safely forgo radical cystectomy without compromising cancer outcomes. The study, published in the Proceedings of the National Academy of Sciences, demonstrates that molecular tools could help redefine treatment for this potentially aggressive form of the disease.

Muscle-invasive bladder cancer is commonly treated with chemotherapy followed by radical cystectomy, a procedure that significantly affects quality of life. However, decades of clinical observations have shown that a substantial percentage of patients have no detectable cancer remaining at the time of surgery, raising critical questions about whether all patients require such aggressive treatment.

Using highly sensitive assays, researchers can detect circulating tumor DNA (ctDNA) in blood and urine tumor DNA (utDNA) in urine to identify traces of residual cancer that may be invisible on scans or biopsies. Investigators analyzed plasma ctDNA and urine utDNA from patients enrolled in a clinical trial evaluating a bladder-sparing treatment strategy. The approach allowed patients who achieved a complete clinical response after tumor biopsy and systemic therapy to forgo immediate bladder removal. The ctDNA and utDNA assays were performed in close collaboration with researchers at Johns Hopkins University, who are among the pioneering researchers who first showed that ctDNA could be used as a measure of measurable residual disease (MRD) in solid tumors.

Among patients who achieved a complete clinical response following systemic therapy, 3-year bladder-intact survival reached 69%, underscoring the potential durability of bladder-sparing treatment strategies in carefully selected individuals. Researchers also found that molecular testing could help predict metastatic risk. Patients with detectable ctDNA prior to systemic therapy faced a significantly higher likelihood of developing metastatic disease. In contrast, only 4.5% of patients with undetectable baseline ctDNA went on to develop metastases, suggesting that ctDNA may serve as a powerful indicator of prognosis.

Importantly, patients with undetectable ctDNA either before or after treatment demonstrated an exceptionally low risk of metastatic recurrence. This finding highlights the potential role of ctDNA monitoring as a tool for identifying patients who may safely avoid radical bladder removal.

The study also showed that plasma and urine DNA testing provide complementary insights. utDNA proved more sensitive than blood-based ctDNA for detecting residual disease confined to the bladder. Detectable utDNA in patients who otherwise appeared to have no evidence of cancer was associated with shorter bladder-intact survival, suggesting that urine-based testing may help uncover hidden cancer not captured by conventional assessments.

Radical cystectomy, while often curative, requires urinary diversion and can profoundly affect daily functioning and quality of life. More precise tools to assess residual disease could help spare some patients from unnecessary surgery while maintaining excellent cancer control.

The researchers emphasized that these results establish a scientific foundation for how ctDNA and utDNA monitoring might be incorporated into clinical decision-making. However, ongoing studies are underway to validate the approach in additional patient cohorts.