Central Nervous System Toxicity in Prostate Cancer Patients Treated with Androgen Receptor Signaling Inhibitors: A Systematic Review, Meta-analysis, and Network Meta-analysis

IF 2.3 3区医学 Q3 ONCOLOGY

Clinical genitourinary cancer Pub Date : 2024-10-24 DOI:10.1016/j.clgc.2024.102251

Akihiro Matsukawa , Takafumi Yanagisawa , Pawel Rajwa , Tamás Fazekas , Marcin Miszczyk , Ichiro Tsuboi , Mehdi Kardoust Parizi , Ekaterina Laukhtina , Jakob Klemm , Sever Chiujdea , Stefano Mancon , Keiichiro Mori , Shoji Kimura , Pierre I. Karakiewicz , Jun Miki , Takahiro Kimura , Shahrokh F. Shariat

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引用次数: 0

Abstract

Background

Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs.

Materials

In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls.

Results

Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue.

Conclusions

The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.

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雄激素受体信号抑制剂治疗前列腺癌患者的中枢神经系统毒性：系统综述、元分析和网络元分析》。

背景：在对晚期/转移性前列腺癌（PCa）患者进行全身治疗时，雄激素受体信号转导抑制剂（ARSIs）能显著提高患者的生存率；然而，可能存在的中枢神经系统（CNS）毒性是一个尚未解决的问题。我们的目的是评估和比较PCa患者接受不同ARSI治疗后继发的中枢神经系统相关不良事件（AEs）的发生率：2023年8月，我们在三个数据库中对接受ARSIs加ADT治疗的PCa患者的随机对照试验（RCT）进行了全面搜索。主要终点包括精神障碍、认知障碍、癫痫发作、疲劳和跌倒：荟萃分析和网络荟萃分析（NMA）共纳入了26项RCT，包括20328名患者。与标准护理（SOC）相比，ARSI增加了精神障碍（RR：1.72；95% CI，1.09-2.71）、认知障碍（RR：2.25；95% CI，1.78-2.86）、癫痫发作（RR：2.20，95% CI，1.09-4.45）、疲劳（RR：1.31，95% CI，1.20-1.43）和跌倒（RR：2.07，95% CI，1.60-2.67）的风险。根据NMAs，恩杂鲁胺显示所有评估的中枢神经系统相关AEs的风险显著增加，而阿比特龙则显示认知障碍、疲劳和跌倒的风险显著增加。相反，除疲劳外，达罗鲁胺没有显示任何中枢神经系统相关AEs的风险显著增加：结论：与SOC相比，在ADT中添加ARSI会增加所有经检查的中枢神经系统相关AEs。每种ARSI都与不同的中枢神经系统相关AE有关。为了使接受ARSI+ADT治疗的PCa患者获得最佳生活质量，有必要谨慎选择患者并监测中枢神经系统后遗症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical genitourinary cancer 医学-泌尿学与肾脏学

CiteScore

5.20

自引率

6.20%

发文量

201

审稿时长

54 days

期刊介绍： Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.