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Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional ⁶⁸GaGa-PSMA-11 PET/CT study
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Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional ⁶⁸GaGa-PSMA-11 PET/CT study
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Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional ⁶⁸GaGa-PSMA-11 PET/CT study
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Journal Article
Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional ⁶⁸GaGa-PSMA-11 PET/CT study
2025
Overview
Background
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).
Methods
122 PCa patients who underwent [⁶⁸Ga]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.
Results
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
< 0.001). CRPC overall survival was independently associated with
LDAH
and PSA (
p
= 0.0168,
p
< 0.001).
Conclusion
The studied meth-ctDNA markers are promising for the minimally-invasive detection and prognostication of CRPC but do not allow for clinical characterization of hsPC. Prospective studies are warranted for their use in therapy response and outcome prediction in CRPC and potential incremental value for PCa monitoring in PSA-low settings.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Antigens
/ Biomarkers, Tumor - genetics
/ Biomedical and Life Sciences
/ cfDNA
/ Circulating Tumor DNA - blood
/ Circulating Tumor DNA - genetics
/ Humans
/ Male
/ Patients
/ PET/CT
/ Positron Emission Tomography Computed Tomography - methods
/ Prostate-Specific Antigen - blood
/ Prostatic Neoplasms - diagnostic imaging
/ Prostatic Neoplasms - genetics
/ PSMA
/ Survival
/ Tumors
