New DNA Tests Offer Hope for Bladder Cancer Patients to Avoid Surgery

For patients diagnosed with muscle-invasive bladder cancer, the standard treatment has traditionally involved radical cystectomy – the complete removal of the bladder. Still, a new study published in the Proceedings of the National Academy of Sciences suggests that ultrasensitive testing of tumor-derived DNA in blood and urine may allow some patients to safely forgo this life-altering surgery without compromising their cancer outcomes.

The Burden of Radical Cystectomy

Muscle-invasive bladder cancer is an aggressive disease often treated with chemotherapy followed by radical cystectomy. While potentially curative, radical cystectomy significantly impacts a patient’s quality of life, requiring urinary diversion and often leading to long-term functional and emotional challenges. Decades of clinical observation have revealed that a substantial number of patients undergoing cystectomy have no detectable cancer remaining at the time of surgery, prompting questions about the necessity of such aggressive treatment for all.

A New Approach: ctDNA and utDNA Testing

Researchers, led by Matthew D. Galsky, MD, Professor of Medicine at the Icahn School of Medicine at Mount Sinai and Deputy Director of the Mount Sinai Tisch Cancer Center, are pioneering a more personalized approach. Their study demonstrates that highly sensitive assays can detect circulating tumor DNA (ctDNA) in blood and urine tumor DNA (utDNA) in urine, identifying traces of residual cancer that may be undetectable through conventional scans or biopsies.

Key Findings from the Study

The study analyzed plasma ctDNA and urine utDNA from patients participating in a clinical trial evaluating a bladder-sparing treatment strategy. The results showed promising outcomes:

• Bladder-Intact Survival: Among patients who achieved a complete clinical response after systemic therapy, the 3-year bladder-intact survival rate reached 69%.
• Predicting Metastatic Risk: Detectable ctDNA before systemic therapy was linked to a significantly higher risk of developing metastatic disease. Conversely, only 4.5% of patients with undetectable baseline ctDNA experienced metastasis.
• Low Risk of Recurrence: Patients with undetectable ctDNA, either before or after treatment, demonstrated a remarkably low risk of metastatic recurrence.
• Complementary Insights: Urine-based utDNA testing proved more sensitive than blood-based ctDNA for detecting residual disease confined to the bladder.

The Power of Combined Testing

“These findings show that blood and urine DNA testing provide complementary information,” explained Dr. Galsky according to Mount Sinai Newsroom. “Together, they offer a powerful new way to identify patients most likely to benefit from bladder preservation.”

Looking Ahead

This research represents a significant step toward personalized care in muscle-invasive bladder cancer. While further validation in larger patient cohorts is underway, the potential to spare select patients from unnecessary surgery while maintaining excellent cancer control is a promising development. As Dr. Galsky stated, “As therapies and diagnostics improve, we must ensure we are not overtreating patients who may already be cured.” (ASCO Post)