Nature Communications (Feb 2024)
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. van Erp,
- Bram De Laere,
- Johan Lindberg,
- Henrik Grönberg,
- Daniel J. Khalaf,
- Matti Annala,
- Kim N. Chi,
- Alexander W. Wyatt
Affiliations
- Nicolette M. Fonseca
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Corinne Maurice-Dror
- Department of Medical Oncology, BC Cancer
- Cameron Herberts
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Wilson Tu
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- William Fan
- Department of Medical Oncology, BC Cancer
- Andrew J. Murtha
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Catarina Kollmannsberger
- Department of Medical Oncology, BC Cancer
- Edmond M. Kwan
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Karan Parekh
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Elena Schönlau
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Cecily Q. Bernales
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Gráinne Donnellan
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Sarah W. S. Ng
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Takayuki Sumiyoshi
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Joanna Vergidis
- Department of Medical Oncology, BC Cancer
- Krista Noonan
- Department of Medical Oncology, BC Cancer
- Daygen L. Finch
- Department of Medical Oncology, BC Cancer
- Muhammad Zulfiqar
- Department of Medical Oncology, BC Cancer
- Stacy Miller
- Department of Radiation Oncology, BC Cancer
- Sunil Parimi
- Department of Medical Oncology, BC Cancer
- Jean-Michel Lavoie
- Department of Medical Oncology, BC Cancer
- Edward Hardy
- Tom McMurtry & Peter Baerg Cancer Centre, Vernon Jubilee Hospital
- Maryam Soleimani
- Department of Medical Oncology, BC Cancer
- Lucia Nappi
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Bernhard J. Eigl
- Department of Medical Oncology, BC Cancer
- Christian Kollmannsberger
- Department of Medical Oncology, BC Cancer
- Sinja Taavitsainen
- Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center
- Matti Nykter
- Prostate Cancer Research Center, Faculty of Medicine and Health Technology, Tampere University and Tays Cancer Center
- Sofie H. Tolmeijer
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Emmy Boerrigter
- Department of Pharmacy, Research Institute for Medical Innovation, Radboud University
- Niven Mehra
- Department of Medical Oncology, Research Institute for Medical Innovation, Radboud University
- Nielka P. van Erp
- Department of Pharmacy, Research Institute for Medical Innovation, Radboud University
- Bram De Laere
- Department of Human Structure and Repair, Ghent University
- Johan Lindberg
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute
- Henrik Grönberg
- Department of Medical Epidemiology and Biostatistics, Karolinska Institute
- Daniel J. Khalaf
- Department of Medical Oncology, BC Cancer
- Matti Annala
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Kim N. Chi
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- Alexander W. Wyatt
- Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia
- DOI
- https://doi.org/10.1038/s41467-024-45475-w
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
