Journal Article

DKFZ-2025-00563

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cell-free DNA aneuploidy score as a dynamic early response marker in prostate cancer.

Isebia, K. T. ; de Jong, A. C. ; van Dessel, L. F. ; de Weerd, V. ; Beaufort, C. ; Helmijr, J. ; Nakauma-González, J. A. ; van Riet, J.DKFZ* ; Hamberg, P. ; Vis, D. ; van der Heijden, M. S. ; Beije, N. ; Lolkema, M. P. ; Deger, T. ; Wilting, S. M. ; de Wit, R. ; Jansen, M. P. H. M. ; Martens, J. W. M.

2025
John Wiley & Sons, Inc. Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/1878-0261.13797

Abstract: Cell-free circulating tumor DNA (ctDNA) has emerged as a promising biomarker for response evaluation in metastatic castration-resistant prostate cancer (mCRPC). The current study evaluated the modified fast aneuploidy screening test-sequencing system (mFast-SeqS), a quick, tumor-agnostic and affordable ctDNA assay that requires a small input of DNA, to generate a genome-wide aneuploidy (GWA) score in mCRPC patients, and correlated this to matched metastatic tumor biopsies. In this prospective multicenter study, GWA scores were evaluated from blood samples of 196 mCRPC patients prior to treatment (baseline) with taxanes (docetaxel and cabazitaxel) and androgen receptor signaling inhibitors (ARSI; abiraterone and enzalutamide), and from 74 mCRPC patients at an early timepoint during treatment (early timepoint; median 21 days). Z-scores per chromosome arm were tested for their association with tumor tissue genomic alterations. We found that a high tumor load in blood (GWAhigh) at baseline was associated with poor response to ARSI [HR: 2.63 (95% CI: 1.86-3.72) P < 0.001] but not to taxanes. Interestingly, GWAhigh score at the early timepoint was associated with poor response to both ARSIs [HR: 6.73 (95% CI: 2.60-17.42) P < 0.001] and taxanes [2.79 (95% CI: 1.34-5.78) P = 0.006]. A significant interaction in Cox proportional hazards analyses was seen when combining GWA status and type of treatment (at baseline P = 0.008; early timepoint P = 0.018). In summary, detection of ctDNA in blood by mFast-SeqS is cheap, fast and feasible, and could be used at different timepoints as a potential predictor for outcome to ARSI and taxane treatment in mCRPC.

Keyword(s): abiraterone ; cabazitaxel ; ctDNA ; docetaxel ; enzalutamide ; prostate cancer

Note: epub

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Contributing Institute(s):

1. Künstl. Intelligenz in der Onkologie (B450)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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