New findings presented at the 2026 ASCO Genitourinary Cancers Symposium suggest that a personalized circulating tumor DNA (ctDNA) test, Signatera, may help identify which people with muscle‑invasive bladder cancer (MIBC) can safely keep their bladder after treatment while maintaining good cancer outcomes. Updated results from two multicenter phase 2 trials, INDIBLADE and RETAIN, showed that ctDNA “clearance” or sustained Signatera‑negativity after neoadjuvant therapy was strongly associated with better survival outcomes, even when patients were managed with bladder‑sparing strategies instead of immediate cystectomy.
In both trials, approximately 73–77% of patients cleared ctDNA following neoadjuvant treatment, and Signatera‑negative status was linked to improved bladder‑intact event‑free survival (BI‑EFS) and metastasis‑free survival (MFS). In INDIBLADE, which evaluated induction dual immune checkpoint blockade followed by chemoradiotherapy as a bladder‑preservation approach for stage II/III MIBC, baseline and post‑neoadjuvant Signatera‑negativity were associated with estimated two‑year BI‑EFS rates approaching or exceeding 90%. In RETAIN, Signatera‑negative patients without clinical or radiographic evidence of disease who were monitored with active surveillance achieved MFS comparable to Signatera‑negative patients who underwent cystectomy, whereas persistent Signatera‑positivity was associated with poor outcomes.
These data support the potential role of tumor‑informed ctDNA testing as a tool to guide response‑adapted, bladder‑sparing treatment decisions in MIBC, though larger randomized studies and longer follow‑up will be needed before this approach becomes standard of care.
References
- Ipilimumab and nivolumab followed by chemoradiotherapy as bladder‑sparing treatment in muscle‑invasive bladder cancer (INDIBLADE). Nature Medicine, 2026.
- Signatera MRD Data at ASCO GU Highlights Potential Utility Across GU Cancers, Including for Bladder Preservation. Company news release, 2026
3. Ghatalia P, Ross EA, Zibelman MR, et al. Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle invasive bladder cancer (MIBC): Integrated analysis of the RETAIN trials. Presented at: 2026 American Society of Clinical Oncology Genitourinary Cancers Symposium. February 26-28, 2026. San Francisco, California. Abstract LBA632. https://meetings.asco.org/meetings/2026-asco-genitourinary-cancers-symposium/334/16924
