Prospective multicenter study of ctDNA versus tumor tissue guiding FGFR-targeted therapy in metastatic urothelial cancer
Fibroblast growth factor receptor (FGFR) alterations are targetable in metastatic urothelial carcinoma (mUC). Identifying FGFR alterations currently requires tissue testing, which is limited by sample availability and cancer heterogeneity. Plasma circulating tumor DNA (ctDNA) offers a complementary testing strategy, but the added value of ctDNA relative to conventional FGFR alteration assessment remains unclear. Here, in a prospective, multicentre study, we show that ctDNA testing has high concordance with tissue FGFR testing and identifies additional actionable FGFR alterations. We profile plasma from 208 patients with mUC undergoing clinical FGFR tissue testing for erdafitinib eligibility. In evaluable baseline samples, FGFR alteration frequency is 26% in either tissue or ctDNA. Among 125 patients with baseline detected ctDNA and paired tissue results, FGFR status is concordant in 90%, and ctDNA has an 84% sensitivity for tissue-detected alterations while also identifying 7 additional cases. Serial plasma collections post-baseline further clarify FGFR status. In 21 patients who received erdafitinib after testing, the median progression-free survival is 7.5 months, and one patient with a ctDNA-exclusive FGFR alteration remained on erdafitinib for 33 months. Our results support clinical uptake of ctDNA FGFR testing in combination with tissue-based approaches in mUC.
Authors
- Daygen L. Finch
- Nimira Alimohamed (ORCID: https://orcid.org/0000-0002-2930-4206)
- Paul Toren (ORCID: https://orcid.org/0000-0002-5762-5787)
- Jean‐Michel Lavoie (ORCID: https://orcid.org/0000-0001-5344-8341)
- Connor Wells
- E. Winquist
- Andreas I. Papadakis (ORCID: https://orcid.org/0000-0003-0026-6581)
- Alexander W. Wyatt (ORCID: https://orcid.org/0000-0003-2399-0329)
- Jussi Nikkola (ORCID: https://orcid.org/0000-0002-5077-2012)
- Gillian Vandekerkhove (ORCID: https://orcid.org/0000-0001-5606-0908)
- M. Ong
- Andrew J. Murtha (ORCID: https://orcid.org/0000-0003-3980-7656)
- Jenny J. Ko (ORCID: https://orcid.org/0000-0002-9286-2673)
- Krista Noonan (ORCID: https://orcid.org/0000-0002-2185-844X)
- Güliz Özgün (ORCID: https://orcid.org/0000-0002-9575-8214)
- David C. Müller (ORCID: https://orcid.org/0000-0001-6471-6065)
- Maria Stephenson
- Lucia Nappi (ORCID: https://orcid.org/0000-0002-4365-7251)
- Kimia Rostin (ORCID: https://orcid.org/0000-0003-3781-0130)
- Dalia Othman
- Cecily Q. Bernales
- Srikala S Sridhar
- Emily Fung
- Jaskirat Atwal
- Reem Merza
- Tarek A. Bismar
- Naveen S. Basappa
- Sunil Parimi
- Bernhard J. Eigl
- Alan Spatz
- Melissa Koudjanian
- Jack V. W. Bacon
- Bryndan Eigl
- Carlos Vasquez-Rios
- Lisa Rebane
- Kim N. Chi
- Elena Schönlau
- Laiba Khan
- Corinne Maurice-Dror
- Gang Wang
- Maryam Soleimani
- Christian Kollmannsberger
Institutions
- University of British Columbia Hospital (CA)
- BC Cancer Agency (CA)
- University of British Columbia (CA)
- University of Alberta (CA)
- Tampere University (FI)
- University of Calgary (CA)
- University of Basel (CH)
- Ottawa Hospital (CA)
- London Health Sciences Centre (CA)
- Jewish General Hospital (CA)
- Spinal Cord Injury BC (CA)
- University Hospital of Basel (CH)
- Princess Margaret Cancer Centre (CA)
- Occupational Cancer Research Centre (CA)
- Canadian Centre for Applied Research in Cancer Control (CA)
- The Prostate Centre (GB)
- Université Laval (CA)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-02-27
- DOI
- https://doi.org/10.1038/s41467-026-69927-7
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Freiwillige Akademische Gesellschaft
- Bladder Cancer Advocacy Network
- Bladder Cancer Canada
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Canadian Institutes of Health Research