Signatera-Based ctDNA Testing Incorporated Into NCCN Bladder Cancer Guidelines
Clinical Summary:
- The NCCN updated its Clinical Practice Guidelines in Oncology for Bladder Cancer to incorporate tumor-informed ctDNA-MRD testing into the management of patients with muscle-invasive bladder cancer following cystectomy.
- The guidelines recommend consideration of FDA-approved tumor-informed ctDNA-MRD testing for risk stratification and selection of adjuvant immunotherapy. The update includes a Category 1 recommendation for ctDNA-guided adjuvant atezolizumab in patients who are ctDNA-MRD positive within 1 year of cystectomy, based on results from the phase 3 IMvigor011 trial.
- This marks the first NCCN recognition of personalized ctDNA-MRD testing as both a prognostic and predictive biomarker in muscle-invasive bladder cancer and further supports the use of MRD-guided treatment strategies in clinical practice.
The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for Bladder Cancer to include tumor-informed circulating tumor DNA (ctDNA) molecular residual disease (MRD) testing as a tool for risk stratification and treatment selection in patients with muscle-invasive bladder cancer.
The updated guidelines recommend consideration of ctDNA-MRD testing following cystectomy in patients who have not previously received immune checkpoint inhibitor therapy using an FDA-approved, personalized, tumor-informed, multiplex PCR next-generation sequencing assay. The recommendation incorporates ctDNA-MRD testing into clinical decision-making regarding adjuvant immunotherapy after surgery.
This update follows results from the phase 3 IMvigor011 trial, which evaluated a ctDNA-guided treatment strategy using the Signatera assay (Natera). Findings from that study supported a Category 1 NCCN recommendation for adjuvant atezolizumab in patients who are ctDNA-MRD positive within 1 year of cystectomy.
“This guideline update marks an important turning point for patients with muscle-invasive bladder cancer,” stated Matthew Galsky, MD, Tisch Cancer Institute at Mount Sinai Medical Center, New York, New York. “For the first time, NCCN has incorporated ctDNA-MRD testing into clinical decision-making following cystectomy.”
The guideline change follows a May 2026 FDA approval of Signatera CDx as a companion diagnostic to identify patients with muscle-invasive bladder cancer who are ctDNA-MRD positive and may benefit from adjuvant immunotherapy.
This marks the third NCCN guideline recommendation involving ctDNA-MRD testing following previous updates in Merkel cell carcinoma and diffuse large B-cell lymphoma.
Source:
Natera. NCCN recommends ctDNA-MRD testing using Signatera™ technology in landmark bladder cancer guideline update. Accessed on June 23, 2026. https://www.natera.com/company/news/nccn-recommends-ctdna-mrd-testing-using-signatera-technology-in-landmark-bladder-cancer-guideline-update/
