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.
Nature communications. 2026 Feb 27 [Epub ahead of print]
David C Müller, Andrew J Murtha, Jack V W Bacon, Maria Stephenson, Connor Wells, Carlos Vasquez-Rios, Kimia Rostin, Lisa Rebane, Elena Schönlau, Jussi Nikkola, Nimira Alimohamed, Naveen S Basappa, Daygen Finch, Jenny J Ko, Jean-Michel Lavoie, Lucia Nappi, Krista Noonan, Michael Ong, Guliz Ozgun, Sunil Parimi, Maryam Soleimani, Srikala S Sridhar, Paul Toren, Eric Winquist, Cecily Q Bernales, Melissa Koudjanian, Jaskirat Atwal, Emily Fung, Laiba Khan, Bryndan Eigl, Dalia Othman, Tarek A Bismar, Gang Wang, Reem Merza, Andreas I Papadakis, Alan Spatz, Christian Kollmannsberger, Corinne Maurice-Dror, Matti Annala, Kim N Chi, Gillian Vandekerkhove, Alexander W Wyatt, Bernhard J Eigl
Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada., Department of Medical Oncology, BC Cancer, Vancouver, BC, Canada., Department of Medical Oncology, Arthur J.E. Child Comprehensive Cancer Centre, Calgary, AB, Canada., Department of Medical Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada., Department of Medical Oncology, BC Cancer, Kelowna, BC, Canada., Department of Medical Oncology, BC Cancer, Abbotsford, BC, Canada., Department of Medical Oncology, BC Cancer, Victoria, BC, Canada., Department of Medical Oncology, BC Cancer, Surrey, BC, Canada., The Ottawa Hospital-Research Institute, Ottawa, ON, Canada., Princess Margaret Cancer Centre, Toronto, ON, Canada., CHU de Québec-Université Laval, Laval University, Quebec City, QC, Canada., Verspeeten Family Cancer Centre at London Health Sciences Centre, London, ON, Canada., Departments of Pathology and Laboratory Medicine, Oncology, Biochemistry and Molecular Biology, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada., Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada., Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Centre, Tampere, Finland., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. ., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. ., Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada. .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41760649