Carrot Aurore, Elaidi Reza-Thierry, Colomban Olivier, Maillet Denis, Tod Michel, You Benoit, Oudard Stéphane
EA3738 CICLY, UCBL-HCL, Faculté de Médecine Lyon-Sud, Université Claude Bernard Lyon 1, 69100 Villeurbanne, France.
Association Pour la Recherche sur les Thérapeutiques en Cancérologie, 20 Rue Leblanc, CEDEX 15, 75908 Paris, France.
Cancers (Basel). 2022 Feb 5;14(3):815. doi: 10.3390/cancers14030815.
In metastatic prostate cancer (PCa) patients, androgen-deprivation therapy (ADT) combined with chemotherapy or next-generation androgen receptor targeted agents is a new standard treatment. The objective of the present study is to assess longitudinal PSA kinetics during treatment using mathematical modeling, to identify the modeled PSA kinetic parameters able to exhibit early prognostic/predictive values.
Phase III clinical trial dataset (NCT00764166) comparing ADT +/- docetaxel in 250 locally treated patients for PCa with rising PSA levels, who were at high risk of metastatic disease was assessed. A kinetic-pharmacodynamic (K-PD) model was used to fit PSA kinetics during the first 100 treatment days, to estimate the modeled PSA production rate K (KPROD) and elimination constant rate K (KELIM). The prognostic value of these parameters, considered as categorized (favorable vs. unfavorable) covariates regarding PSA progression-free survival (PSA-PFS) and overall survival (OS), was assessed using univariate/multivariate analyses.
Data from 177/250 patients was assessed. KELIM exhibited a significant prognostic value regarding PSA-PFS and KPROD regarding OS (univariate analysis). In the PSA-PFS final multivariate model, KELIM and the primary therapy type were significant. The OS multivariate model integrated both KPROD and baseline PSA doubling-time.
In this first study assessing the modeled PSA kinetics prognostic value in PCa patients treated with systemic treatments, KELIM and KPROD exhibited respective prognostic values regarding PSA-PFS and OS.
在转移性前列腺癌（PCa）患者中，雄激素剥夺疗法（ADT）联合化疗或新一代雄激素受体靶向药物是一种新的标准治疗方法。本研究的目的是使用数学模型评估治疗期间前列腺特异性抗原（PSA）的纵向动力学，以确定能够显示早期预后/预测价值的建模PSA动力学参数。
评估了一项III期临床试验数据集（NCT00764166），该数据集比较了250例局部治疗的PSA水平升高且有高转移疾病风险的PCa患者接受ADT±多西他赛的情况。使用动力学-药效学（K-PD）模型拟合前100个治疗日期间的PSA动力学，以估计建模的PSA产生率K（KPROD）和消除常数率K（KELIM）。使用单变量/多变量分析评估这些参数作为关于PSA无进展生存期（PSA-PFS）和总生存期（OS）的分类（有利与不利）协变量的预后价值。
评估了177/250例患者的数据。KELIM对PSA-PFS具有显著的预后价值，KPROD对OS具有显著的预后价值（单变量分析）。在PSA-PFS最终多变量模型中，KELIM和主要治疗类型具有显著性。OS多变量模型纳入了KPROD和基线PSA倍增时间。
在第一项评估全身治疗的PCa患者中建模的PSA动力学预后价值的研究中，KELIM和KPROD分别对PSA-PFS和OS具有预后价值。
