Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.
Shanghai Genitourinary Cancer Institute, Shanghai, China.
Eur J Nucl Med Mol Imaging. 2023 May;50(6):1822-1832. doi: 10.1007/s00259-023-06123-5. Epub 2023 Jan 31.
The aim of this study was to evaluate the impact of the spatial heterogeneity of prostate-specific membrane antigen (PSMA) uptake on circulating tumor DNA (ctDNA) characteristics and the response rate to new hormonal agent (NHA) treatment.
This retrospective study included 153 patients with metastatic castration-resistant prostate cancer (mCRPC) who underwent gallium-68 [ Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) and ctDNA sequencing with a less than 2-week interval. SUVhetero was defined as the variance of SUVmean for each PSMA-positive lesion. SUVmax-mean was obtained by subtracting the SUVmax by the SUVmean. Patients receiving abiraterone treatment after [ Ga]Ga-PSMA-11 PET/CT and ctDNA sequencing and with complete follow-up record were included into prostate-specific antigen (PSA) response rate analysis. PSA response was defined as a reduction of greater than 50% from baseline.
The ctDNA detection rate was 65% (100/153). Higher SUVhetero value contributed to higher ctDNA% (Spearman's rho = 0.278, p < 0.002). A total of 60 patients were included in PSA response rate analysis. The median follow-up was 19.3 (IQR 16.2-23.2) months. Compare to patients with higher SUVhetero value, patients with NA SUVhetero had a higher PSA response rate (52% vs. 90%, p = 0.036). A higher SUVmax-mean value was strongly correlated with higher SUVhetero (Spearman's rho = 0.833, p < 0.0001). Patients with higher SUVmax-mean value also had a higher PSA response rate compared to patients with lower SUVmax-mean value (83.3% vs. 53.3%, p = 0.024). An external cohort confirmed baseline SUVmax-mean value was associated with enzalutamide treatment response rate. Patients with alterations in AR, DNA damage repair pathway, TP53, AR-associated pathway, cell cycle pathway, or WNT pathway had higher SUVmax-mean value compared to those without (p < 0.05).
Spatial heterogeneity of the PSMA uptake was associated with ctDNA characteristics and response rate to NHA treatment.
本研究旨在评估前列腺特异性膜抗原（PSMA）摄取的空间异质性对循环肿瘤 DNA（ctDNA）特征和新激素治疗（NHA）反应率的影响。
本回顾性研究纳入了 153 例接受镓-68[Ga]Ga-PSMA-11 正电子发射断层扫描/计算机断层扫描（PET/CT）和 ctDNA 测序的转移性去势抵抗性前列腺癌（mCRPC）患者，两次检查的时间间隔小于 2 周。SUVhetero 定义为每个 PSMA 阳性病灶 SUVmean 的方差。SUVmax-mean 通过减去 SUVmax 得到 SUVmean。对接受 Ga-PSMA-11 PET/CT 和 ctDNA 测序后接受阿比特龙治疗且有完整随访记录的患者进行前列腺特异性抗原（PSA）反应率分析。PSA 反应定义为基线时 PSA 降低大于 50%。
ctDNA 检测率为 65%（100/153）。较高的 SUVhetero 值与较高的 ctDNA%相关（Spearman's rho=0.278，p<0.002）。共纳入 60 例 PSA 反应率分析患者。中位随访时间为 19.3（IQR 16.2-23.2）个月。与 SUVhetero 值较高的患者相比，SUVhetero 值较低的患者 PSA 反应率更高（52%比 90%，p=0.036）。较高的 SUVmax-mean 值与较高的 SUVhetero 呈强相关（Spearman's rho=0.833，p<0.0001）。与 SUVmax-mean 值较低的患者相比，SUVmax-mean 值较高的患者 PSA 反应率更高（83.3%比 53.3%，p=0.024）。外部队列证实基线 SUVmax-mean 值与恩扎卢胺治疗反应率相关。与无改变的患者相比，AR、DNA 损伤修复途径、TP53、AR 相关途径、细胞周期途径或 WNT 途径发生改变的患者 SUVmax-mean 值更高（p<0.05）。
PSMA 摄取的空间异质性与 NHA 治疗的 ctDNA 特征和反应率相关。
