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

Kilian Kluge, Holger Einspieler, David Haberl, Clemens Spielvogel, Stefan Stoiber, Chrysoula Vraka, Laszlo Papp, Sabine Wunsch, Gerda Egger, Gero Kramer, Bernhard Grubmüller, Shahrokh Shariat, Marcus Hacker, Lukas Kenner, Alexander Haug*

*Corresponding author for this work

Research output: Journal article (peer-reviewed)Journal article


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.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalJournal of Nuclear Medicine
Issue number1
Early online date30 Nov 2023
Publication statusPublished - 01 Jan 2024


  • Aged
  • Biomarkers
  • Cell-Free Nucleic Acids
  • Edetic Acid
  • Gallium Isotopes
  • Gallium Radioisotopes
  • Hormones
  • Humans
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography/methods
  • Prognosis
  • Prospective Studies
  • Prostatic Neoplasms, Castration-Resistant/diagnostic imaging
  • Prostatic Neoplasms/diagnostic imaging
  • Retrospective Studies
  • Tumor Burden
  • prostate cancer
  • PSMA
  • PET/CT
  • cell-free DNA
  • liquid biopsy

ASJC Scopus subject areas

  • Radiology, Nuclear Medicine and Imaging


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