Prospective multicenter study of ctDNA versus tumor tissue guiding FGFR-targeted therapy in metastatic urothelial cancer

作者：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 L. Finch, Jenny J. Ko, Jean‐Michel Lavoie, Lucia Nappi, Krista Noonan, M. Ong, Güliz Özgün, Sunil Parimi, Maryam Soleimani, Srikala S Sridhar, Paul Toren, E. Winquist, Cecily Q. Bernales, Melissa Koudjanian, Jaskirat Atwal, Emily Fung, Laiba Khan, Bryndan Eigl, 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., Gillian Vandekerkhove, Alexander W. Wyatt, Bernhard J. Eigl, Bernhard J. Eigl · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-69927-7 · 被引用次数：1 · 研究领域：Cancer Genomics and Diagnostics、Bladder and Urothelial Cancer Treatments、Fibroblast Growth Factor Research

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. Plasma ctDNA testing for FGFR alterations in metastatic urothelial carcinoma shows high concordance with tissue...