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

Fonseca, Nicolette M., Maurice-Dror, Corinne, Herberts, Cameron, Tu, Wilson, Fan, William, Murtha, Andrew J., Kollmannsberger, Catarina, Kwan, Edmond M. +31 more·2024·Nature Communications
DOI 10.1038/s41467-024-45475-wPMC PMC10902374
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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.

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  • In advanced prostate cancer, ctDNA fraction correlates with disease burden and predicts survival and treatment outcomes across therapeutic contexts.

    “In advanced prostate cancer, ctDNA fraction correlates with disease burden and predicts survival and treatment outcomes across therapeutic contexts, suggesting that liquid biopsy can contribute not only to genotyping but also to risk stratification and test triage [19].”

    From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [19]

  • Contemporary studies demonstrate that ctDNA can complement tissue sequencing, identify non-overlapping clinically relevant alterations, and capture dynamic tumor evolution during treatment.

    “Contemporary studies demonstrate that circulating tumor DNA (ctDNA) can complement tissue sequencing, identify non-overlapping clinically relevant alterations, and capture dynamic tumor evolution during treatment [18, 19].”

    From A decision-oriented framework for genomic testing across the prostate cancer continuum (2026) · cites this paper as [19]

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Authors
Fonseca, N. M., Maurice-Dror, C., Herberts, C., Tu, W., Fan, W., Murtha, A. J., Kollmannsberger, C., Kwan, E. M., Parekh, K., Schönlau, E., Bernales, C. Q., Donnellan, G., Ng, S. W. S., Sumiyoshi, T., Vergidis, J., Noonan, K., Finch, D. L., Zulfiqar, M., Miller, S., Parimi, S., Lavoie, J.-M., Hardy, E., Soleimani, M., Nappi, L., Eigl, B. J., Kollmannsberger, C., Taavitsainen, S., Nykter, M., Tolmeijer, S. H., Boerrigter, E., Mehra, N., van Erp, N. P., De Laere, B., Lindberg, J., Grönberg, H., Khalaf, D. J., Annala, M., Chi, K. N., & Wyatt, A. W.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2024-02-28
Volume
15
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-024-45475-w
PMC
PMC10902374
Cited by
148
References
6
Language
en
Licence
Funders
Canadian Cancer Society Challenge Grant

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