Conteduca Vincenza, Scarpi Emanuela, Matteucci Federica, Caroli Paola, Ravaglia Giorgia, Fantini Lorenzo, Gurioli Giorgia, Schepisi Giuseppe, Wetterskog Daniel, Menna Cecilia, Burgio Salvatore Luca, Lolli Cristian, Paganelli Giovanni, Attard Gerhardt, De Giorgi Ugo
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
University College London Cancer Institute, London, UK.
JCO Precis Oncol. 2019 Dec;3:1-13. doi: 10.1200/PO.18.00302.
Biomarkers for treatment personalization in metastatic castration-resistant prostate cancer (mCRPC) could help improve patient outcomes. Multiple tests on blood have reported associations with poorer outcome, including serum lactate dehydrogenase (LDH), chromogranin A (CGA), neutrophil:lymphocyte ratio (NLR), and, recently, copy number (CN) of androgen receptor (AR) in plasma DNA. Biologic data suggest an association between choline uptake and AR signaling. We aimed to integrate 18-fluorocholine (FCH) uptake on positron emission tomography/computed tomography (PET/CT) scanning with plasma CN and other routinely obtained circulating biomarkers to evaluate their association with outcome.
We determined plasma CN by digital droplet polymerase chain reaction from 105 mCRPC samples collected before abiraterone (n = 65) or enzalutamide (n = 40) therapy in the before (n = 26) and after (n = 79) chemotherapy settings. Pretreatment serum LDH, CGA, and NLR were also measured. FCH-PET/CT scan was performed at baseline, and maximum standardized uptake value (SUV), total lesion activity (TLA), and metabolic tumor volume (MTV) were calculated. Main end points were the correlation of FCH-PET/CT parameters with circulating biomarkers and their impact on outcome.
Plasma CN gain was observed in 27 patients (25.7%), and it correlated significantly with higher median SUV, TLA, and MTV values ( < .001). Kaplan-Meier curves showed significantly worse progression-free survival and overall survival in patients with plasma gain and higher SUV, TLA, and MTV values ( < .001 in each prognostic group). Conversely, no association was reported for prostate-specific antigen response. On multivariable analysis of overall survival, we showed as independent factors gain (hazard ratio [HR], 1.92; 95% CI, 1.07 to 3.47; = .029), presence of visceral metastasis (HR, 3.04; 95% CI, 1.66 to 5.58; = < .001), LDH (HR, 2.95; 95% CI, 1.72 to 5.05; < .001), NLR (HR, 3.51; 95% CI, 2.14 to 5.74; < .001), serum CGA (HR, 3.36; 95% CI, 1.99 to 5.67; < .001), and MTV (HR, 2.09; 95% CI, 1.25 to 3.50; = .005).
Our results indicate the potential usefulness of integrating functional imaging with plasma DNA analysis and other noninvasive biomarkers as a tool to improve treatment selection for CRPC. A larger prospective evaluation is warranted.
转移性去势抵抗性前列腺癌（mCRPC）治疗个体化的生物标志物有助于改善患者预后。多项血液检测报告显示与较差预后相关，包括血清乳酸脱氢酶（LDH）、嗜铬粒蛋白A（CGA）、中性粒细胞与淋巴细胞比值（NLR），以及最近血浆DNA中雄激素受体（AR）的拷贝数（CN）。生物学数据表明胆碱摄取与AR信号传导之间存在关联。我们旨在将正电子发射断层扫描/计算机断层扫描（PET/CT）扫描中的18-氟胆碱（FCH）摄取与血浆CN及其他常规获得的循环生物标志物相结合，以评估它们与预后的关联。
我们通过数字液滴聚合酶链反应，对105份mCRPC样本的血浆CN进行了测定，这些样本是在阿比特龙（n = 65）或恩杂鲁胺（n = 40）治疗前（n = 26）和化疗前后（n = 79）收集的。还测量了治疗前的血清LDH、CGA和NLR。在基线时进行FCH-PET/CT扫描，并计算最大标准化摄取值（SUV）、总病灶活性（TLA）和代谢肿瘤体积（MTV）。主要终点是FCH-PET/CT参数与循环生物标志物的相关性及其对预后的影响。
27例患者（25.7%）出现血浆CN增加，且与较高的中位SUV、TLA和MTV值显著相关（P <.001）。Kaplan-Meier曲线显示，血浆CN增加以及SUV、TLA和MTV值较高的患者，其无进展生存期和总生存期显著更差（每个预后组P <.001）。相反，未报告与前列腺特异性抗原反应相关。在总生存期的多变量分析中，我们显示血浆CN增加（风险比[HR]，1.92；95%置信区间，1.07至3.47；P =.029）、存在内脏转移（HR，3.04；95%置信区间，1.66至5.58；P <.001）、LDH（HR，2.95；95%置信区间，1.72至5.05；P <.001）、NLR（HR，3.51；95%置信区间，2.14至5.74；P <.001）、血清CGA（HR，3.36；95%置信区间，1.99至5.67；P <.001）和MTV（HR，2.09；95%置信区间，1.25至3.50；P =.005）为独立因素。
我们的结果表明，将功能成像与血浆DNA分析及其他非侵入性生物标志物相结合，作为改善CRPC治疗选择的工具具有潜在用途。有必要进行更大规模的前瞻性评估。
