Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer

Gillian Vandekerkhove, Jean-Michel Lavoie, Matti Annala, Andrew J. Murtha, Nora Sundahl, Simon Walz, Takeshi Sano, Sinja Taavitsainen, Elie Ritch, Ladan Fazli, Antonio Hurtado-Coll, Gang Wang, Matti Nykter, Peter C. Black, Tilman Todenhöfer, Piet Ost, Ewan A. Gibb, Kim N. Chi, Bernhard J. Eigl () and Alexander W. Wyatt ()
Additional contact information
Gillian Vandekerkhove: University of British Columbia
Jean-Michel Lavoie: BC Cancer
Matti Annala: University of British Columbia
Andrew J. Murtha: University of British Columbia
Nora Sundahl: Ghent University Hospital
Simon Walz: University Hospital Tübingen
Takeshi Sano: University of British Columbia
Sinja Taavitsainen: Tampere University and Tays Cancer Centre
Elie Ritch: University of British Columbia
Ladan Fazli: University of British Columbia
Antonio Hurtado-Coll: University of British Columbia
Gang Wang: BC Cancer
Matti Nykter: Tampere University and Tays Cancer Centre
Peter C. Black: University of British Columbia
Tilman Todenhöfer: Studienpraxis Urologie
Piet Ost: Ghent University Hospital
Ewan A. Gibb: Decipher Biosciences, Inc.
Kim N. Chi: University of British Columbia
Bernhard J. Eigl: BC Cancer
Alexander W. Wyatt: University of British Columbia

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.

Date: 2021
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DOI: 10.1038/s41467-020-20493-6

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