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Updated: Sep 9, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Comparative neurological safety of novel hormonal therapies in advanced prostate cancer: a Bayesian network
Ganesh Bushi1, Aftab Ullah2,3, Urooj Khan4
1Department of Pharmacy Practice, Faculty of Pharmacy, M. S. Ramaiah University of Applied Sciences, Bangalore, 560054, India.
Background:
Novel hormonal agents (NHAs), including enzalutamide, abiraterone acetate, apalutamide, and darolutamide, have improved survival in advanced prostate cancer (PCa). However, their potential neurological adverse effects (AEs)-notably cognitive impairment, seizures, and falls-raise safety concerns, particularly in older adults. This study aimed to compare the neurological safety profiles of NHAs in men with advanced PCa using a Bayesian network meta-analysis (NMA).
Methods:
We conducted a systematic review and Bayesian NMA following PRISMA-NMA guidelines. Comprehensive searches of PubMed, EMBASE, and Web of Science were completed through May 21, 2025. Eligible randomized controlled trials (RCTs) compared NHAs plus androgen deprivation therapy (ADT) with placebo, ADT, or other NHAs. Neurological AEs of interest included cognitive impairment, falls, and seizures. Bayesian random-effects models were used to calculate risk ratios (RRs) with 95% credible intervals (CrIs). Treatments were ranked using surface under the cumulative ranking curve (SUCRA) values.
Results:
Twenty-five RCTs with over 19,000 patients were included. No treatments showed a statistically significant increased risk of neurological AEs. Enzalutamide had the highest estimated risk for cognitive impairment (RR 3.88; 95% CrI, 0.697-22.1) and seizures (RR 13.8; 95% CrI, 0.983-1.07 × 103), although not statistically significant. Darolutamide and nonsteroidal antiandrogens exhibited the most favorable neurological safety profiles across outcomes based on SUCRA rankings.
Conclusion:
Although no NHA significantly increased neurological AEs, enzalutamide showed the highest estimated risk, while darolutamide and NSAAs ranked best for neurological safety. Darolutamide may be preferred in elderly patients, highlighting the need for further long-term safety data.
Insights
Novel hormonal agents (NHAs) for advanced prostate cancer (PCa) show no significant neurological risks. Enzalutamide had the highest estimated risk, while darolutamide and nonsteroidal antiandrogens (NSAAs) demonstrated the best neurological safety profiles.
Area of Science:
- Oncology
- Neuroscience
- Pharmacology
Background:
- Novel hormonal agents (NHAs) improve survival in advanced prostate cancer (PCa).
- Neurological adverse effects (AEs) like cognitive impairment, seizures, and falls are safety concerns with NHAs, especially in older adults.
- This study compares the neurological safety of NHAs in advanced PCa patients.
Purpose of the Study:
- To compare the neurological safety profiles of novel hormonal agents (NHAs) in men with advanced prostate cancer (PCa).
- To evaluate risks of cognitive impairment, seizures, and falls associated with NHAs.
- To inform clinical decision-making regarding NHA selection, particularly for elderly patients.
Main Methods:
- A systematic review and Bayesian network meta-analysis (NMA) following PRISMA-NMA guidelines.
- Searched PubMed, EMBASE, and Web of Science for eligible randomized controlled trials (RCTs) up to May 21, 2025.
- Analyzed neurological AEs (cognitive impairment, falls, seizures) using Bayesian random-effects models and ranked treatments by SUCRA values.
Main Results:
- Twenty-five RCTs involving over 19,000 patients were analyzed.
- No NHA demonstrated a statistically significant increased risk of neurological AEs.
- Enzalutamide showed the highest estimated risk for cognitive impairment and seizures, though not statistically significant. Darolutamide and NSAAs had the most favorable neurological safety profiles.
Conclusions:
- While no NHA significantly increased neurological AEs, enzalutamide presented the highest estimated risk.
- Darolutamide and nonsteroidal antiandrogens (NSAAs) ranked highest for neurological safety.
- Darolutamide may be a preferred option for elderly patients, emphasizing the need for more long-term safety data.
