Department of Oncology, Cambridge Memorial Hospital, Cambridge, Ontario, Canada.
G. d'Annunzio University of Chieti, Dept. of Medical, Oral and Biotechnological Sciences, "SS. Annunziata" Hospital, Urology Unit, Chieti, Italy; ASL Abruzzo 2, Dept. of Urology, Chieti, Italy.
J Geriatr Oncol. 2021 Jun;12(5):687-695. doi: 10.1016/j.jgo.2020.11.002. Epub 2020 Nov 22.
Novel androgen receptor axis-targeting drugs (ARATs) have been shown to improve outcomes in men with prostate cancer. Central nervous system androgen blockade may be harmful for older adults who may be at increased risk of adverse cognitive and psychologic effects.
To systematically evaluate the effect of ARATs on cognition and depression in men with metastatic prostate cancer.
We searched PubMed and EMBASE for articles published in English between September 2012 and September 2019 reporting cognition and depression outcomes in men receiving ARATs for metastatic prostate cancer using validated psychometric tools. The level of evidence and risk of bias were assessed using the GRADE approach for randomized clinical trials and observational studies.
15 reports studying 8954 men with metastatic castration-sensitive and -resistant, or non-metastatic castration-resistant prostate cancer were identified. Data were available for abiraterone, enzalutamide and apalutamide but not darolutamide. The mean (and 95% confidence interval) and median (and min-max) of the absolute scores and changes from baseline were included, when available. There was heterogeneity in the psychometric tools used which obviated statistical pooling of results. Very limited data assessing cognition suggested that abiraterone was associated with improved cognitive functioning or perhaps less cognitive harm versus enzalutamide. Fourteen reports assessed emotional wellbeing. ARATs reduced depressive symptoms when compared to prednisone alone or placebo but not compared to bicalutamide. Abiraterone may improve short-term emotional functioning relative to enzalutamide. The quality of evidence was low when examining ARAT effect on cognitive function and moderate when examining ARAT effect on depression.
Depression was assessed more frequently than cognition in men receiving ARATs. Self-reported depression measures favored abiraterone over enzalutamide and both abiraterone and enzalutamide over placebo. Data evaluating apalutamide and darolutamide are lacking. Further studies of ARATs using validated clinician-based psycho-cognition tools along with self-reported measures in men with metastatic prostate cancer are needed.
新型雄激素受体轴靶向药物（ARATs）已被证明可改善前列腺癌患者的预后。中枢神经系统雄激素阻断可能对老年人有害，因为他们可能面临更多的认知和心理不良影响的风险。
系统评估 ARATs 对转移性前列腺癌男性认知和抑郁的影响。
我们在 PubMed 和 EMBASE 上搜索了 2012 年 9 月至 2019 年 9 月期间发表的英文文章，这些文章使用经过验证的心理计量工具报告了接受 ARATs 治疗转移性前列腺癌的男性的认知和抑郁结果。使用随机临床试验和观察性研究的 GRADE 方法评估证据水平和偏倚风险。
确定了 15 项研究，共纳入 8954 名转移性去势敏感和去势抵抗型或非转移性去势抵抗型前列腺癌男性。可获得阿比特龙、恩扎鲁胺和阿帕鲁胺的数据，但无达拉鲁胺的数据。当可用时，包括了绝对值和基线变化的平均值（和 95%置信区间）和中位数（和最小-最大）。使用的心理计量工具存在异质性，因此排除了结果的统计学汇总。评估认知功能的非常有限的数据表明，与恩扎鲁胺相比，阿比特龙可能与认知功能改善或认知损害减少相关。14 项报告评估了情绪健康。与单独使用泼尼松或安慰剂相比，ARATs 可降低抑郁症状，但与比卡鲁胺相比则没有。与恩扎鲁胺相比，阿比特龙可能会改善短期情绪功能。检查 ARAT 对认知功能的影响时证据质量较低，而检查 ARAT 对抑郁的影响时证据质量为中等。
在接受 ARATs 治疗的男性中，抑郁的评估频率高于认知。与恩扎鲁胺相比，自我报告的抑郁测量方法更倾向于阿比特龙，与安慰剂相比，阿比特龙和恩扎鲁胺都更有优势。缺乏评估阿帕鲁胺和达罗鲁胺的数据。需要进一步研究 ARATs，在转移性前列腺癌男性中使用经过验证的基于临床医生的心理认知工具以及自我报告的测量方法。
