Should we treat this patient as having metastatic prostate cancer?

Treatment for Metastatic Prostate Cancer

Yes, patients with metastatic prostate cancer should be treated with systemic therapy targeting metastatic disease, as this approach offers significant survival benefits compared to localized treatment alone. 1

First-Line Treatment Options for Metastatic Prostate Cancer

Androgen Deprivation Therapy (ADT) as Foundation

• Continuous ADT remains the backbone of treatment for metastatic hormone-naïve prostate cancer 1, 2
• When starting treatment with an LHRH agonist, an antiandrogen should be given for 3-4 weeks to prevent testosterone flare 2, 3

Combination Therapy with ADT

• ADT plus docetaxel or ADT plus abiraterone are both recommended as first-line treatment options for metastatic hormone-naïve prostate cancer, offering superior survival outcomes compared to ADT alone 1
• The strongest evidence for docetaxel benefit is in men with high-volume disease (CHAARTED criteria) 1
• Similar survival benefits are seen with abiraterone acetate in high-risk patients (LATITUDE criteria) and in the metastatic population in the STAMPEDE trial 1
• The recommended docetaxel regimen is six doses administered every 3 weeks at 75 mg/m² 1, 4

Treatment Selection Considerations

Factors to Guide Treatment Choice

• ADT plus abiraterone and ADT plus docetaxel have not been directly compared, and it is unknown if certain patients benefit more from one regimen versus the other 1
• Selection between docetaxel and abiraterone should consider:
  • Fitness for chemotherapy 1
  • Patient comorbidities 1
  • Toxicity profiles of each agent 1
  • Quality of life considerations 1
  • Drug availability and cost 1

Disease Volume/Risk Considerations

• For high-volume disease: Stronger evidence supports docetaxel addition to ADT 1
• For high-risk disease: Abiraterone shows significant survival benefits 1

Progression to Castration-Resistant Prostate Cancer

• If disease progresses to castration-resistant prostate cancer (CRPC), several treatment options are available:
  • Abiraterone or enzalutamide for asymptomatic/mildly symptomatic men with chemotherapy-naïve metastatic CRPC 1, 2
  • Docetaxel for men with metastatic CRPC 1, 2
  • Radium-223 for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases 1, 2
  • Cabazitaxel for patients previously treated with docetaxel 5

Supportive Care for Bone Metastases

• A single fraction of external beam radiotherapy is recommended for palliation of painful bone metastases 2
• In patients with bone metastases from CRPC at high risk for clinically significant skeletal-related events, denosumab or zoledronic acid should be considered 2
• MRI of the spine to detect subclinical cord compression is recommended in men with CRPC with vertebral metastases 2

Important Caveats and Monitoring

• Regular exercise should be recommended for men starting ADT as it reduces fatigue and improves quality of life 2
• Patients receiving ADT should be monitored with clinical assessment and PSA measurement, as well as management of side effects 2
• Men on long-term ADT should be monitored for side effects including osteoporosis and metabolic syndrome 2
• PSA is not always a reliable indicator of disease activity in patients with undifferentiated (anaplastic) metastatic prostate cancer with neuroendocrine features 2
• Patients with evidence of neuroendocrine changes should receive chemotherapy in addition to ADT 2