Comparison of discovery rates and prognostic utility of [68Ga]Ga-PSMA-11 PET/CT and circulating tumor DNA in prostate cancer—a cross-sectional study,European Journal of Nuclear Medicine and Molecular Imaging

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Comparison of discovery rates and prognostic utility of [68Ga]Ga-PSMA-11 PET/CT and circulating tumor DNA in prostate cancer—a cross-sectional study
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : 2024-05-02 , DOI: 10.1007/s00259-024-06698-7
Kilian Kluge , Holger Einspieler , David Haberl , Clemens Spielvogel , Dominik Amereller , Gerda Egger , Gero Kramer , Bernhard Grubmüller , Shahrokh Shariat , Marcus Hacker , Lukas Kenner , Alexander Haug

Background

Circulating-tumor DNA (ctDNA) and prostate-specific membrane antigen (PSMA) ligand positron-emission tomography (PET) enable minimal-invasive prostate cancer (PCa) detection and survival prognostication. The present study aims to compare their tumor discovery abilities and prognostic values.

Methods

One hundred thirty men with confirmed PCa (70.5 ± 8.0 years) who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) imaging and plasma sample collection (March 2019–August 2021) were included. Plasma-extracted cell-free DNA was subjected to whole-genome-based ctDNA analysis. PSMA-positive tumor lesions were delineated and their quantitative parameters extracted. ctDNA and PSMA PET/CT discovery rates were compared, and the prognostic value for overall survival (OS) was evaluated.

Results

PSMA PET discovery rates according to castration status and PSA ranges did differ significantly (P = 0.013, P < 0.001), while ctDNA discovery rates did not (P = 0.311, P = 0.123). ctDNA discovery rates differed between localized and metastatic disease (P = 0.013). Correlations between ctDNA concentrations and PSMA-positive tumor volume (PSMA-TV) were significant in all (r = 0.42, P < 0.001) and castration-resistant (r = 0.65, P < 0.001), however not in hormone-sensitive patients (r = 0.15, P = 0.249). PSMA-TV and ctDNA levels were associated with survival outcomes in the Logrank (P < 0.0001, P < 0.0001) and multivariate Cox regression analysis (P = 0.0023, P < 0.0001).

Conclusion

These findings suggest that PSMA PET imaging outperforms ctDNA analysis in detecting prostate cancer across the whole spectrum of disease, while both modalities are independently highly prognostic for survival outcomes.

Graphical Abstract

中文翻译：

[68Ga]Ga-PSMA-11 PET/CT 和循环肿瘤 DNA 在前列腺癌中的发现率和预后效用的比较——一项横断面研究

背景

循环肿瘤 DNA (ctDNA) 和前列腺特异性膜抗原 (PSMA) 配体正电子发射断层扫描 (PET) 可实现微创前列腺癌 (PCa) 检测和生存预测。本研究旨在比较他们的肿瘤发现能力和预后价值。

方法

纳入了130 名确诊为 PCa 的男性（70.5 ± 8.0 岁），他们接受了 [ ⁶⁸ Ga]Ga-PSMA-11 PET/CT (184.8 ± 19.7 MBq) 成像和血浆样本采集（2019 年 3 月至 2021 年 8 月）。对血浆提取的游离 DNA 进行基于全基因组的 ctDNA 分析。描绘出 PSMA 阳性肿瘤病灶并提取其定量参数。比较 ctDNA 和 PSMA PET/CT 发现率，并评估总生存 (OS) 的预后价值。

结果

根据去势状态和 PSA 范围的 PSMA PET 发现率确实存在显着差异（P = 0.013，P < 0.001 ），而 ctDNA 发现率则没有显着差异（P = 0.311，P = 0.123）。局部疾病和转移性疾病的 ctDNA 发现率不同 ( P = 0.013)。 ctDNA 浓度与 PSMA 阳性肿瘤体积 (PSMA-TV) 之间的相关性在所有患者 ( r = 0.42，P < 0.001) 和去势抵抗患者 ( r = 0.65，P < 0.001) 中均显着相关，但在激素敏感患者中则不显着 ( r = 0.15，P = 0.249）。 PSMA-TV 和 ctDNA 水平与 Logrank（ P < 0.0001，P < 0.0001）和多变量 Cox 回归分析（P = 0.0023，P < 0.0001）中的生存结果相关。