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Peer-ReviewedPubMedResearch ArticleTherapeuticClinical genitourinary cancer · 2026

Risk Factors and Treatment Outcomes in Metastatic Prostate Cancer With Brain Metastases.

Xu VE, Wang J, Bernardo RC, Wang M, Whalen MJ, Jain M (+4 more)

Abstract

IntroductionProstate cancer with brain metastases (PCBM) is rare and carries a poor prognosis. However, the risk factors and optimal treatment strategies for PCBM are poorly understood.Patient and methodsThe National Cancer Database (NCDB) was queried for patients diagnosed with metastatic prostate cancer (mPCa) from 2010 to 2021. Demographics, tumor characteristics, and treatments were compared between patients with and without PCBM. PCBM incidence and risk factors were assessed with temporal analysis and multivariable logistic regression. Overall survival (OS) was analyzed using Kaplan-Meier and Cox proportional hazards models. Subgroup analyses examined combinations of systemic and local treatments including surgery of metastasis sites, whole brain radiation (WBRT), and stereotactic radiosurgery (SRS).ResultsOf 101,900 patients with mPCa, 1144 (1.1%) had PCBM. No significant temporal increase in PCBM incidence was observed. Neuroendocrine (NE) histology (aOR: 3.92, 95%CI: 1.09-14.13), liver metastases (aOR: 2.86, 95%CI: 1.68-8.84), and other peripheral organ metastases (aOR: 2.47, 95%CI: 1.10-5.54) were independently associated with PCBM risk. Patients with PCBM had worse OS (15.1 vs 32.6 months, P ConclusionPCBM is associated with aggressive disease features such as NE histology. Durable survival appears primarily dependent on systemic disease control, with local therapies potentially offering additional benefit in select cases. These findings underscore the need for molecular stratification and advocate for the inclusion of PCBM patients in future clinical trials.

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