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

Author

Listed:
  • 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
    BC Cancer
    School of Clinical Sciences; Monash University)

  • 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
    Kyoto University)

  • 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
    BC Cancer)

  • 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
    Radboud University)

  • Emmy Boerrigter

    (Radboud University)

  • Niven Mehra

    (Radboud University)

  • Nielka P. Erp

    (Radboud University)

  • Bram Laere

    (Ghent University
    Ghent University
    Karolinska Institute)

  • Johan Lindberg

    (Karolinska Institute)

  • Henrik Grönberg

    (Karolinska Institute)

  • Daniel J. Khalaf

    (BC Cancer)

  • Matti Annala

    (University of British Columbia
    Tampere University and Tays Cancer Center)

  • Kim N. Chi

    (University of British Columbia
    BC Cancer)

  • Alexander W. Wyatt

    (University of British Columbia
    Michael Smith Genome Sciences Centre, BC Cancer)

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.

Suggested Citation

  • 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. Bern, 2024. "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45475-w
    DOI: 10.1038/s41467-024-45475-w
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    References listed on IDEAS

    as
    1. Viktor A. Adalsteinsson & Gavin Ha & Samuel S. Freeman & Atish D. Choudhury & Daniel G. Stover & Heather A. Parsons & Gregory Gydush & Sarah C. Reed & Denisse Rotem & Justin Rhoades & Denis Loginov & , 2017. "Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
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    3. Cameron Herberts & Matti Annala & Joonatan Sipola & Sarah W. S. Ng & Xinyi E. Chen & Anssi Nurminen & Olga V. Korhonen & Aslı D. Munzur & Kevin Beja & Elena Schönlau & Cecily Q. Bernales & Elie Ritch , 2022. "Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer," Nature, Nature, vol. 608(7921), pages 199-208, August.
    4. 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 Wa, 2021. "Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
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