Conteduca Vincenza, Casadei Chiara, Scarpi Emanuela, Brighi Nicole, Schepisi Giuseppe, Lolli Cristian, Gurioli Giorgia, Toma Ilaria, Poti Giulia, Farolfi Alberto, De Giorgi Ugo
IRCCS Istituto Romagnolo Per Lo Studio Dei Tumori (IRST) "Dino Amadori", via Piero Maroncelli 40, 47014 Meldola, Italy.
Department of Medical and Surgical Sciences, Unit of Medical Oncology and Biomolecular Therapy, University of Foggia, Policlinico Riuniti, 71122 Foggia, Italy.
Cancers (Basel). 2022 Apr 29;14(9):2219. doi: 10.3390/cancers14092219.
Background: Baseline high circulating tumor DNA (ctDNA) fraction in plasma and androgen receptor (AR) copy number (CN) gain identify mCRPC patients with worse outcomes. This study aimed to assess if ctDNA associates with PSA kinetics. Methods: In this prospective biomarker study, we evaluate ctDNA fraction and AR CN from plasma samples. We divided patients into high and low ctDNA level and in AR gain and AR normal. Results: 220 baseline samples were collected from mCRPC treated with abiraterone (n = 140) or enzalutamide (n = 80). A lower rate of PSA decline ≥ 50% was observed in patients with high ctDNA (p = 0.017) and AR gain (p = 0.0003). Combining ctDNA fraction and AR CN, we found a different median PSA progression-free survival (PFS) among four groups: (1) low ctDNA/AR normal, (2) high ctDNA/AR normal, (3) low ctDNA/AR gain, and (4) high ctDNA/AR gain (11.4 vs. 5.0 vs. 4.8 vs. 3.7 months, p < 0.0001). In a multivariable analysis, high ctDNA, AR gain, PSA DT, PSA DT velocity remained independent predictors of PSA PFS. Conclusions: Elevated ctDNA levels and AR gain are negatively and independently correlated with PSA kinetics in mCRPC men treated with abiraterone or enzalutamide.
血浆中循环肿瘤DNA（ctDNA）基线高比例以及雄激素受体（AR）拷贝数增加可识别出预后较差的转移性去势抵抗性前列腺癌（mCRPC）患者。本研究旨在评估ctDNA是否与前列腺特异性抗原（PSA）动力学相关。方法：在这项前瞻性生物标志物研究中，我们评估了血浆样本中的ctDNA比例和AR拷贝数。我们将患者分为ctDNA水平高和低以及AR增加和AR正常两组。结果：从接受阿比特龙（n = 140）或恩杂鲁胺（n = 80）治疗的mCRPC患者中收集了220份基线样本。ctDNA高的患者（p = 0.017）和AR增加的患者（p = 0.0003）中观察到PSA下降≥50%的比例较低。结合ctDNA比例和AR拷贝数，我们发现四组患者的中位PSA无进展生存期（PFS）不同：（1）低ctDNA/AR正常，（2）高ctDNA/AR正常，（3）低ctDNA/AR增加，（4）高ctDNA/AR增加（11.4个月对5.0个月对4.8个月对3.7个月，p < 0.0001）。在多变量分析中，高ctDNA、AR增加、PSA倍增时间（DT）、PSA DT速度仍然是PSA PFS的独立预测因素。结论：在接受阿比特龙或恩杂鲁胺治疗的mCRPC男性中，ctDNA水平升高和AR增加与PSA动力学呈负相关且独立相关。
