Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [??Ga]Ga-PSMA-11 PET/CT study

Kilian Kilian; Vincent Lotz; Holger Einspieler; David Haberl; Clemens Spielvogel; Dominik Amereller; Gero Kramer; Bernhard Grubmüller; Shahrokh Shariat; Alexander Haug; Marcus Hacker; Lukas Kenner; Gerda Egger

doi:10.1186/s13148-025-01811-5

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Title (eng)

Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [??Ga]Ga-PSMA-11 PET/CT study

Author

Kilian Kilian

Vincent Lotz

Holger Einspieler

David Haberl

Clemens Spielvogel

Dominik Amereller

Gero Kramer

Bernhard Grubmüller

Shahrokh Shariat

Alexander Haug

Marcus Hacker

Lukas Kenner

University of Veterinary Medicine Vienna

Gerda Egger

Abstract (eng)

To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).122 PCa patients who underwent [??Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried. PET scans were qualitatively and quantitatively assessed. PSA and meth-ctDNA markers were compared to PET findings, and their relative prognostic value was evaluated.PSA discriminated best between negative and tumor-indicative PET scans in all (AUC 0.77) and hormone-sensitive (hsPC) patients (0.737). In castration-resistant PCa (CRPC), the meth-ctDNA marker KLF8 performed best (AUC 0.824). CHST11 differentiated best between non- and metastatic scans (AUC 0.705) overall, KLF8 best in hsPC and CRPC (AUC 0.662, 0.85). Several meth-ctDNA markers correlated low to moderate with the tumor volume in all (5/8) and CRPC patients (6/8), while PSA levels correlated moderately to strongly with the tumor volume in all groups (all p?

Keywords (eng)

HumansMalePositron Emission Tomography Computed Tomography MethodsAgedDNA Methylation GeneticsProstatic Neoplasms GeneticsProstatic Neoplasms BloodProstatic Neoplasms Diagnostic ImagingGallium RadioisotopesMiddle AgedBiomarkers, Tumor GeneticsBiomarkers, Tumor BloodProstate-Specific Antigen BloodProstate-Specific Antigen GeneticsGallium IsotopesCross-Sectional StudiesCirculating Tumor DNA GeneticsCirculating Tumor DNA BloodPrognosisAged, 80 and overProstatic NeoplasmsCastration-Resistant GeneticsCastration-Resistant BloodCastration-Resistant Diagnostic ImagingEdetic Acidanalogs & Derivatives

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:4004

DOI

10.1186/s13148-025-01811-5

Is in series

Title (eng)

Clinical Epigenetics

Volume