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Background <p>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).</p> Methods <p>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.</p> Results <p>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 <i>KLF8</i> performed best (AUC 0.824). <i>CHST11</i> differentiated best between non- and metastatic scans (AUC 0.705) overall, <i>KLF8</i> 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 <i>p</i> &lt; 0.001). CRPC overall survival was independently associated with <i>LDAH</i> and PSA (<i>p</i> = 0.0168, <i>p</i> &lt; 0.001).</p> Conclusion <p>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.</p>

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Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [⁶⁸Ga]Ga-PSMA-11 PET/CT study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月25日

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

摘要

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.