Molecular markers may help guide bladder-sparing treatment strategies in MIBC

Data published in Proceedings of the National Academy of Science provide the conceptual framework for incorporating circulating tumor DNA (ctDNA) and urinary tumor DNA (utDNA) assays into clinical decision-making regarding the need for cystectomy in patients with muscle-invasive bladder cancer (MIBC).¹

Notably, the study showed that the molecular markers could identify patients with an extremely low risk of metastasis following systemic therapy, supporting the potential use of these tools in determining which patients may safely forego cystectomy without compromising cancer outcomes.

“Our goal is to move beyond a one-size-fits-all approach,” said lead author Matthew D. Galsky, MD, professor of medicine (hematology and medical oncology) at the Icahn School of Medicine and Deputy Director of the Mount Sinai Tisch Cancer Center, in a news release on the results.² “We are working toward a future where treatment decisions are guided by precise molecular tools that tell us which patients truly need surgery, and which patients may be cured without losing their bladder.”

The study included patients who were enrolled in a clinical trial evaluating a bladder-sparing treatment strategy. Patients who achieved a clinical complete response after tumor biopsy and systemic therapy were able to forego immediate bladder removal.

Among those with a clinical complete response following 4 rounds of systemic therapy, the 3-year bladder-intact survival was 69%.

Molecular testing also showed potential in predicting metastatic risk. Overall, the risk of metastasis was significantly higher among those with detectable vs undetectable ctDNA before initiating systemic therapy (HR, 4.68; 95% CI, 1.10 to 43.35; log-rank P = .036). Undetectable ctDNA before or after receipt of systemic therapy was associated with an extremely low risk of metastasis. Importantly, only 4.5% of patients who had undetectable ctDNA at baseline went on to develop metastatic disease.

The investigators also observed that urine utDNA was more sensitive than plasma ctDNA at detecting residual disease within the bladder. In patients with a clinical complete response, detectable urine utDNA was associated with a shorter bladder-intact survival (HR, 6.47; 95% CI, 1.34 to 31.31; log-rank P = .008).

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

According to the authors, these findings lay the groundwork for further investigation into how these molecular tools may be incorporated into clinical decision-making. Studies are underway to validate this approach in additional patient cohorts, according to the news release from Mount Sinai.²

“This research represents an important step toward personalized care in muscle-invasive bladder cancer,” Galsky concluded in the release.² “As therapies and diagnostics improve, we must ensure we are not overtreating patients who may already be cured.”

REFERENCES

1. Galsky MD, Izadmehr S, Yu M, et al. Monitoring of plasma and urine tumor-derived DNA to inform bladder-sparing approaches for patients with muscle-invasive bladder cancer. Proc Natl Acad Sci U S A. 2026;123(8):e2533449123. doi:10.1073/pnas.2533449123

2. Mount Sinai study may help cancer patients keep their bladder. News release. The Mount Sinai Hospital / Mount Sinai School of Medicine. February 19, 2026. Accessed February 20, 2026. https://www.mountsinai.org/about/newsroom/2026/mount-sinai-study-may-help-cancer-patients-keep-their-bladder