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

A. Matsukawa, T. Yanagisawa, P. Rajwa, T. Fazekas, M. Miszczyk, I. Tsuboi, MK. Parizi, E. Laukhtina, J. Klemm, S. Chiujdea, S. Mancon, K. Mori, S. Kimura, PI. Karakiewicz, J. Miki, T. Kimura, SF. Shariat

. 2025 ; 23 (1) : 102251. [pub] 20241024

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, systematický přehled, metaanalýza, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/bmc25010093

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.

Citace poskytuje Crossref.org

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$a BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) significantly improve survival in systemic therapy for advanced/metastatic prostate cancer (PCa) patients; however possible central nervous system (CNS) toxicity is an unaddressed concern. We aimed to assess and compare the incidence of CNS-related adverse events (AEs) secondary to the treatment of PCa patients with different ARSIs. MATERIALS: In August 2023, a comprehensive seach was conducted in three databases for randomized controlled trials (RCTs) of PCa patients receiving ARSIs plus ADT. The primary endpoints included mental impairment, cognitive impairment, seizure, fatigue, and falls. RESULTS: Twenty-six RCTs, comprising 20,328 patients, were included in meta-analyses and network meta-analyses (NMAs). ARSIs increased the risk of mental impairment (RR: 1.72; 95% CI, 1.09-2.71), cognitive impairment (RR: 2.25; 95% CI, 1.78-2.86), seizure (RR: 2.20, 95% CI, 1.09-4.45), fatigue (RR: 1.31, 95% CI, 1.20-1.43), and falls (RR: 2.07, 95% CI, 1.60-2.67) compared to standard of care (SOC). Based on NMAs, Enzalutamide showed a significant increase in risk for all assessed CNS-related AEs, while Abiraterone demonstrated significant risk increases in cognitive impairment, fatigue, and falls. Conversely, Darolutamide did not exhibit significant increases in risk for any CNS-related AEs, except for fatigue. CONCLUSIONS: The addition of ARSIs to ADT increased all examined CNS-related AEs compared to SOC. Each ARSI is associated with a distinct profile of CNS-related AEs. Careful patient selection and monitoring for CNS sequelae is necessary to achieve the best quality of life in patients on ARSI + ADT for PCa.
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$a Yanagisawa, Takafumi $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Rajwa, Pawel $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland
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$a Fazekas, Tamás $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary
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$a Miszczyk, Marcin $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Collegium Medicum - Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland
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$a Tsuboi, Ichiro $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan
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$a Parizi, Mehdi Kardoust $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shariati Hospital, Tehran University of Medical Science, Tehran, Iran
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$a Laukhtina, Ekaterina $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
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$a Klemm, Jakob $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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$a Chiujdea, Sever $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Spitalul Clinic Judetean Murures, University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Mures, Romania
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$a Mancon, Stefano $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
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$a Mori, Keiichiro $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Kimura, Shoji $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Karakiewicz, Pierre I $u Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montréal Health Center, Montréal, QC, Canada
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$a Miki, Jun $u Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Kimura, Takahiro $u Department of Urology, The Jikei University School of Medicine, Tokyo, Japan
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$a Shariat, Shahrokh F $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Research Center for Evidence Medicine, Tabriz University of Medical Science, Tabriz, Iran. Electronic address: shahrokh.shariat@meduniwien.ac.at
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