Bladder cancer guideline update includes Signatera™-guided care
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Signatera™ for Muscle-Invasive Bladder Cancer (MIBC)
Personalized ctDNA testing to risk-stratify patients, inform treatment decisions, and detect molecular recurrence earlier than standard tools.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Include a NCCN Category 1 Recommendation for ctDNA-MRD Guided Adjuvant Therapy in Muscle-Invasive Bladder Cancer
The National Comprehensive Cancer Network® (NCCN®) updated its NCCN Guidelines® for Bladder Cancer (Version 2.2026) to include ctDNA-MRD testing as a recommended tool for guiding adjuvant therapy decisions in patients with muscle-invasive bladder cancer following cystectomy.
The updated NCCN Guidelines include the following:
- Algorithm Placement (BL-7 & BL-G 1 of 8)
- Adjuvant atezolizumab is now a Category 1, Other Recommended treatment option for patients who test ctDNA-MRD positive within one year following radical cystectomy.
- Biomarker Recognition (BL-I 2 of 3)
- The NCCN Bladder Cancer Panel formally recognizes personalized, tumor-informed ctDNA as both a prognostic and predictive biomarker after cystectomy, and recommends considering ctDNA-MRD testing as a tool for risk stratification and to guide adjuvant immunotherapy decisions in patients who have not received prior immune checkpoint inhibitor treatment.
- Defined Assay Criteria
- The NCCN Guidelines specify that ctDNA-MRD status must be determined by an FDA-approved, personalized, tumor-informed multiplex PCR-NGS assay for ctDNA.
Signatera™ is a personalized, tumor-informed ctDNA test built on a multiplex PCR-NGS platform, meeting the assay criteria specified in the NCCN Guidelines.
First and only randomized phase 3 trial supporting ctDNA-guided treatment in MIBC
IMvigor011 demonstrated improved outcomes with a ctDNA-guided treatment approach in muscle-invasive bladder cancer.
ctDNA+ patients
benefit from adjuvant immunotherapy
36%
lower risk of recurrence or death.1
ctDNA– patients
may avoid unnecessary treatment
95%
disease-free at 1 year with observation alone.2
Detect recurrence
earlier than imaging
96
days earlier detection of relapse.3
IMvigor011 trial results
- ctDNA-positive patients had improved DFS vs placebo.
- Median DFS: 9.9 vs 4.8 months (HR 0.64).
- Reduced risk of death by 41% (HR 0.59).
Supports ctDNA-guided treatment escalation in high-risk MIBC.
Clinical decision points for Signatera™ across the MIBC continuum
Phase 3 evidence supporting Signatera™ in MIBC
Phase 3 and perioperative studies support the clinical utility of personalized ctDNA testing in MIBC.
IMvigor011
Persistently ctDNA-negative patients demonstrated favorable outcomes with surveillance alone:
- OS: 100% at 12 months; 98% at 18 months¹
- DFS: 92% at 12 months; 88% at 18 months¹
NIAGARA
ctDNA status remained highly prognostic in patients receiving perioperative immunotherapy:
- ctDNA-negative patients had significantly improved outcomes²
- ctDNA negativity after cystectomy was associated with a 91% lower risk of relapse²
- ctDNA clearance during treatment correlated with improved event-free survival²
CheckMate274
ctDNA identified patients most likely to benefit from adjuvant nivolumab:
- Median DFS: 52.1 vs 5.0 months by ctDNA status³
- ctDNA-positive patients derived greater benefit from nivolumab³
Explore real-world cases
Post-Surgical MRD Assessment
Persistent ctDNA positivity after cystectomy identified residual disease and supported initiation of adjuvant nivolumab:
- ctDNA levels decreased after surgery but remained detectable
- ctDNA declined further after adjuvant immunotherapy
Recurrence Monitoring
Serial ctDNA monitoring detected molecular recurrence before radiographic progression:
- Median lead time over imaging: 96 days²
- ctDNA detected recurrence in 13 of 17 patients after cystectomy²
Immunotherapy Response Monitoring
ctDNA dynamics helped clarify treatment response during pembrolizumab therapy:
- Imaging initially suggested progression while ctDNA levels decreased
- Pembrolizumab treatment was continued
- ctDNA clearance preceded radiographic resolution³
Is Signatera™ for MIBC right for your patients?
References
1Powles T, et al. ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer (IMvigor011). New England Journal of Medicine. 2025.
2Powles T, et al. IMvigor011: Phase 3 study of ctDNA-guided adjuvant atezolizumab in muscle-invasive bladder cancer. Presented at ESMO 2025.
3Christensen E, et al. Early detection of metastatic relapse and monitoring of therapeutic efficacy by ultra-deep sequencing of plasma cell-free DNA in patients with urothelial bladder carcinoma. Journal of Clinical Oncology. 2019;37(18):1547–1557.
4Sfakianos JP, et al. Association of tumor-informed circulating tumor DNA detectability before and after radical cystectomy with disease-free survival in patients with bladder cancer. European Urology Oncology. 2025.
5Powles T, et al. Circulating tumor DNA in patients with muscle-invasive bladder cancer receiving perioperative durvalumab (NIAGARA). Presented at ASCO 2025.
Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.2.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed June 26, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.