Examining the Relationship and Prognostic Significance of Cell-Free DNA Levels and the PSMA-Positive Tumor Volume in Men with Prostate Cancer: A Retrospective-Prospective [68Ga]Ga-PSMA-11 PET/CT Study
Jazyk angličtina Země Spojené státy americké Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Odkazy
PubMed
38050125
PubMed Central
PMC10755525
DOI
10.2967/jnumed.123.266158
PII: jnumed.123.266158
Knihovny.cz E-zdroje
- Klíčová slova
- PET/CT, PSMA, cell-free DNA, liquid biopsy, prostate cancer,
- MeSH
- biologické markery MeSH
- EDTA MeSH
- hormony MeSH
- izotopy gallia MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * diagnostické zobrazování MeSH
- nádory prostaty * diagnostické zobrazování patologie MeSH
- PET/CT metody MeSH
- prognóza MeSH
- prospektivní studie MeSH
- radioizotopy galia MeSH
- retrospektivní studie MeSH
- senioři MeSH
- tumor burden MeSH
- volné cirkulující nukleové kyseliny * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- EDTA MeSH
- hormony MeSH
- izotopy gallia MeSH
- PSMA-11 MeSH Prohlížeč
- radioizotopy galia MeSH
- volné cirkulující nukleové kyseliny * MeSH
Functional imaging with prostate-specific membrane antigen (PSMA) ligands has emerged as the standard imaging method for prostate cancer (PCA). In parallel, the analysis of blood-derived, cell-free DNA (cfDNA) has been shown to be a promising quantitative biomarker of PCA aggressiveness and patient outcome. This study aimed to evaluate the relationship and prognostic value of cfDNA concentrations and the PSMA-positive tumor volume (PSMA-TV) in men with PCA undergoing [68Ga]Ga-PSMA-11 PET/CT imaging. Methods: We recruited 148 men with histologically proven PCA (mean age, 70.7 ± 7.7 y) who underwent [68Ga]Ga-PSMA-11 PET/CT (184.9 ± 18.9 MBq) and blood sampling between March 2019 and August 2021. Among these, 74 (50.0%) had hormone-sensitive PCA and 74 (50.0%) had castration-resistant PCA (CRPC). All patients provided written informed consent before blood sample collection and imaging. The cfDNA was extracted and quantified, and PSMA-expressing tumor lesions were delineated to extract the PSMA-TVs. The Spearman coefficient assessed correlations between PSMA-TV and cfDNA concentrations and cfDNA's relation with clinical parameters. The Kruskal-Wallis test examined the mean cfDNA concentration differences based on PSMA-TV quartiles for significantly correlated patient groups. Log-rank and multivariate Cox regression analyses evaluated the prognostic significance of high and low cfDNA and PSMA-TV levels for overall survival. Results: Weak positive correlations were found between cfDNA concentration and PSMA-TV in the overall group (r = 0.16, P = 0.049) and the CRPC group (r = 0.31, P = 0.007) but not in hormone-sensitive PCA patients (r = -0.024, P = 0.837). In the CRPC cohort, cfDNA concentrations significantly differed between PSMA-TV quartiles 4 and 1 (P = 0.002) and between quartiles 4 and 2 (P = 0.016). Survival outcomes were associated with PSMA-TV (P < 0.0001, P = 0.004) but not cfDNA (P = 0.174, P = 0.12), as per the log-rank and Cox regression analysis. Conclusion: These findings suggest that cfDNA might serve as a biomarker of advanced, aggressive CRPC but does not reliably reflect total tumor burden or prognosis. In comparison, [68Ga]Ga-PSMA-11 PET/CT provides a highly granular and prognostic assessment of tumor burden across the spectrum of PCA disease progression.
Center for Medical Physics and Biomedical Engineering Medical University of Vienna Vienna Austria
Christian Doppler Laboratory for Applied Metabolomics Medical University of Vienna Vienna Austria
Department of Pathology Medical University of Vienna Vienna Austria
Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic; and
Department of Urology and Andrology University Hospital Krems Krems Austria
Department of Urology Medical University of Vienna Vienna Austria
Department of Urology University of Texas Southwestern Medical Center Dallas Texas
Department of Urology Weill Cornell Medical College New York New York
Division of Urology Department of Special Surgery University of Jordan Amman Jordan
Karl Landsteiner Institute of Urology and Andrology Vienna Austria
Karl Landsteiner University of Health Sciences Krems Austria
Fettke H, Ng N, Hauser C, et al. . Circulating tumor DNA and outcomes with lutetium-PSMA in advanced prostate cancer: preliminary results from an Australian study [abstract]. Cancer Res. 2022;82(suppl):532.