Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer

Nicolette M. Fonseca, Corinne Maurice-Dror, Cameron Herberts, Wilson Tu, William Fan, Andrew J. Murtha, Catarina Kollmannsberger, Edmond M. Kwan, Karan Parekh, Elena Schönlau, Cecily Q. Bernales, Gráinne Donnellan, Sarah W. S. Ng, Takayuki Sumiyoshi, Joanna Vergidis, Krista Noonan, Daygen L. Finch, Muhammad Zulfiqar, Stacy Miller, Sunil Parimi, Jean-Michel Lavoie, Edward Hardy, Maryam Soleimani, Lucia Nappi, Bernhard J. Eigl, Christian Kollmannsberger, Sinja Taavitsainen, Matti Nykter, Sofie H. Tolmeijer, Emmy Boerrigter, Niven Mehra, Nielka P. Erp, Bram Laere, Johan Lindberg, Henrik Grönberg, Daniel J. Khalaf, Matti Annala (), Kim N. Chi () and Alexander W. Wyatt ()
Additional contact information
Nicolette M. Fonseca: University of British Columbia
Corinne Maurice-Dror: BC Cancer
Cameron Herberts: University of British Columbia
Wilson Tu: University of British Columbia
William Fan: BC Cancer
Andrew J. Murtha: University of British Columbia
Catarina Kollmannsberger: BC Cancer
Edmond M. Kwan: University of British Columbia
Karan Parekh: University of British Columbia
Elena Schönlau: University of British Columbia
Cecily Q. Bernales: University of British Columbia
Gráinne Donnellan: University of British Columbia
Sarah W. S. Ng: University of British Columbia
Takayuki Sumiyoshi: University of British Columbia
Joanna Vergidis: BC Cancer
Krista Noonan: BC Cancer
Daygen L. Finch: BC Cancer
Muhammad Zulfiqar: BC Cancer
Stacy Miller: BC Cancer
Sunil Parimi: BC Cancer
Jean-Michel Lavoie: BC Cancer
Edward Hardy: Tom McMurtry & Peter Baerg Cancer Centre, Vernon Jubilee Hospital
Maryam Soleimani: BC Cancer
Lucia Nappi: University of British Columbia
Bernhard J. Eigl: BC Cancer
Christian Kollmannsberger: BC Cancer
Sinja Taavitsainen: Tampere University and Tays Cancer Center
Matti Nykter: Tampere University and Tays Cancer Center
Sofie H. Tolmeijer: University of British Columbia
Emmy Boerrigter: Radboud University
Niven Mehra: Radboud University
Nielka P. Erp: Radboud University
Bram Laere: Ghent University
Johan Lindberg: Karolinska Institute
Henrik Grönberg: Karolinska Institute
Daniel J. Khalaf: BC Cancer
Matti Annala: University of British Columbia
Kim N. Chi: University of British Columbia
Alexander W. Wyatt: University of British Columbia

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract No consensus strategies exist for prognosticating metastatic castration-resistant prostate cancer (mCRPC). Circulating tumor DNA fraction (ctDNA%) is increasingly reported by commercial and laboratory tests but its utility for risk stratification is unclear. Here, we intersect ctDNA%, treatment outcomes, and clinical characteristics across 738 plasma samples from 491 male mCRPC patients from two randomized multicentre phase II trials and a prospective province-wide blood biobanking program. ctDNA% correlates with serum and radiographic metrics of disease burden and is highest in patients with liver metastases. ctDNA% strongly predicts overall survival, progression-free survival, and treatment response independent of therapeutic context and outperformed established prognostic clinical factors. Recognizing that ctDNA-based biomarker genotyping is limited by low ctDNA% in some patients, we leverage the relationship between clinical prognostic factors and ctDNA% to develop a clinically-interpretable machine-learning tool that predicts whether a patient has sufficient ctDNA% for informative ctDNA genotyping (available online: https://www.ctDNA.org ). Our results affirm ctDNA% as an actionable tool for patient risk stratification and provide a practical framework for optimized biomarker testing.

Date: 2024
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DOI: 10.1038/s41467-024-45475-w

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