What is the best course of treatment for a patient with prostate (prostate) cancer that has metastasized to the brain?

Management of Prostate Cancer with Brain Metastases

The recommended treatment for prostate cancer with brain metastases should include local therapy (surgery or radiation therapy) for brain lesions in addition to systemic therapy for metastatic prostate cancer, regardless of the systemic therapy used for the primary disease. 1

Initial Assessment and Management

• Brain metastases from prostate cancer are rare, occurring in fewer than 1% of metastatic prostate cancer cases 2
• MRI with gadolinium enhancement is the preferred diagnostic imaging modality for brain metastases due to its higher sensitivity in detecting multiple lesions 3
• Dexamethasone should be initiated for symptomatic brain metastases at 4-8 mg/day for moderate symptoms, increasing to 16 mg/day for severe symptoms with marked mass effect 3

Local Therapy for Brain Metastases

Surgical Management

• Surgery is recommended for patients with:
  • Large tumors with significant mass effect 1, 3
  • Symptomatic lesions refractory to steroids 1
  • Diagnostic uncertainty requiring tissue confirmation 1
  • Solitary accessible brain metastases 1

Radiation Therapy Options

• For patients with 1-4 unresected brain metastases, stereotactic radiosurgery (SRS) alone should be offered 1, 3
• For patients with resected brain metastases, SRS to the surgical cavity is recommended 3
• Whole brain radiation therapy (WBRT) may be considered for multiple brain metastases not amenable to surgery or SRS 4
• When WBRT is used, hippocampal avoidance and memantine should be considered to reduce neurocognitive decline in patients with expected survival of 4 months or more 3

Systemic Therapy for Metastatic Prostate Cancer

Hormone-Sensitive Metastatic Prostate Cancer

• Continuous androgen deprivation therapy (ADT) is recommended as first-line treatment for metastatic hormone-naive disease 1
• ADT plus docetaxel is recommended for patients fit enough for chemotherapy 1

Castration-Resistant Prostate Cancer (CRPC)

• For asymptomatic/mildly symptomatic men with chemotherapy-naïve metastatic CRPC, abiraterone or enzalutamide are recommended 1
• For men with bone-predominant, symptomatic metastatic CRPC without visceral metastases, radium-223 is recommended 1
• Docetaxel is recommended for men with metastatic CRPC 1
• In the post-docetaxel setting, abiraterone, enzalutamide, cabazitaxel, and radium-223 (in those without visceral disease) are recommended options 1

Special Considerations for Brain Metastases in Prostate Cancer

• Patients with brain metastases from prostate cancer typically have advanced disease with other concurrent metastases, particularly bone (94%) and lymph nodes (63%) 5
• Median overall survival after brain metastasis diagnosis is approximately 9.4 months 5
• Treatment modalities for brain metastases (surgery with adjuvant radiation, SRS, or WBRT) show similar survival outcomes in prostate cancer patients 5
• Brain metastases in prostate cancer often present with neurological symptoms (54%) and radiographic brain edema (57%), but seizures are less common (7%) 5

Management Algorithm

1. Diagnosis and Assessment:

   • Confirm brain metastases with gadolinium-enhanced MRI 3
   • Assess number, size, and location of brain lesions 1
   • Evaluate patient's neurological symptoms and performance status 1

2. Immediate Management:

   • Start dexamethasone for symptomatic patients or those with significant edema 3
   • Consider anti-seizure medications only if seizures have occurred (not prophylactically) 3

3. Local Therapy Decision:

   • For 1-4 brain metastases: Consider surgery for large, symptomatic lesions or SRS for smaller lesions 1
   • For multiple (>4) brain metastases: Consider WBRT 4
   • For post-surgical cases: SRS to the surgical cavity 3

4. Systemic Therapy Decision:

   • For hormone-sensitive disease: ADT with or without docetaxel 1
   • For castration-resistant disease: Abiraterone, enzalutamide, docetaxel, or radium-223 based on patient characteristics 1

Common Pitfalls and Caveats

• Brain metastases from prostate cancer are rare and may be misdiagnosed as primary brain tumors if thorough investigations are not performed 2
• Enzalutamide has epileptogenic potential and may need to be suspended in patients with brain metastases, especially those with seizures 6
• Drug interactions between systemic therapies for prostate cancer and treatments for brain metastases should be carefully monitored 6
• Despite their rarity, brain metastases should not be overlooked in prostate cancer patients with neurological symptoms, even with relatively low PSA levels 2