Initial results of a recent clinical trial revealed that tumor resection and systemic therapy achieved lasting remissions for some patients with muscle-invasive bladder cancer (MIBC), indicating that not all patients require complete removal of the bladder, or cystectomy, which can have lasting consequences for urinary and sexual function. The cancer, however, recurred in a subset of patients who initially underwent the more limited procedure without cystectomy. Researchers led by Ludwig Johns Hopkins’ Yuxuan Wang, Co-director Bert Vogelstein and Matthew Galsky of the Icahn School of Medicine at Mount Sinai, New York, conducted a long-term follow-up of trial enrollees to determine whether tumor DNA in the plasma (ctDNA) or urine (utDNA) could serve as biomarkers to inform prognosis and need for cystectomy. They reported in a February issue of PNAS that three-year survival with intact bladders for patients who had a complete clinical response following tumor resection and systemic therapy was 69%. Risk of metastasis was nearly five-fold higher for those with detectable ctDNA prior to systemic therapy, while undetectable ctDNA before or after systemic therapy was associated with extremely low metastatic risk. utDNA was more sensitive than ctDNA in detecting residual disease within the bladder, and detectable utDNA despite complete clinical response was associated with shorter bladder-intact survival. The findings are a first step toward incorporating ut/ctDNA assays in the management of MIBC.
Monitoring of plasma and urine tumor-derived DNA to inform bladder-sparing approaches for patients with muscle-invasive bladder cancer
PNAS, 2026 February 18