Treatment Options for Prostate Cancer Metastasis
The recommended first-line treatment for metastatic hormone-naïve prostate cancer is continuous androgen deprivation therapy (ADT), with the addition of docetaxel chemotherapy for patients fit enough to receive it. 1
First-Line Treatment for Metastatic Prostate Cancer
Hormone-Naïve Metastatic Disease
- Continuous ADT is the standard first-line treatment for metastatic hormone-naïve prostate cancer 1
- When starting treatment with an LHRH agonist, an antiandrogen should be given for 3-4 weeks to prevent testosterone flare 1, 2
- ADT plus docetaxel is recommended as first-line treatment for metastatic hormone-naïve disease in men fit enough for chemotherapy 1
- Bilateral orchiectomy provides rapid testosterone reduction within 12-24 hours and is a valid option for patients with severe symptoms requiring immediate relief 2
- Regular exercise should be recommended for men starting ADT as it reduces fatigue and improves quality of life 1
Intermittent vs. Continuous ADT
- Intermittent ADT is not recommended for metastatic hormone-naïve prostate cancer outside of clinical trials, unless there is significant intolerance to hormone therapy 1
- Intermittent ADT is recommended for men with biochemical relapse after radical radiotherapy starting ADT 1
Treatment of Castration-Resistant Prostate Cancer (CRPC)
First-Line Options for CRPC
- Abiraterone or enzalutamide are recommended for asymptomatic/mildly symptomatic men with chemotherapy-naïve metastatic CRPC 1
- Docetaxel (75 mg/m² every 3 weeks with prednisone 5 mg twice daily) is recommended for men with metastatic CRPC 1, 3
- Radium-223 is recommended for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases 1
- Sipuleucel-T is an option in asymptomatic/mildly symptomatic patients with chemotherapy-naïve metastatic CRPC 1
Post-Docetaxel Options
- In patients with metastatic CRPC who have progressed after docetaxel, recommended options include abiraterone, enzalutamide, cabazitaxel, and radium-223 (in those without visceral disease) 1
Supportive Care for Bone Metastases
- A single fraction of external beam radiotherapy is recommended for palliation of painful bone metastases 1
- In patients with bone metastases from CRPC at high risk for clinically significant skeletal-related events, denosumab or zoledronic acid can be recommended 1
- MRI of the spine to detect subclinical cord compression is recommended in men with CRPC with vertebral metastases 1
- Urgent MRI of the spine is very strongly recommended in men with CRPC with vertebral metastases and neurological symptoms to detect cord compression 1
Monitoring During Treatment
- Patients receiving ADT should be monitored with clinical assessment and PSA measurement, as well as management of side effects 1
- Initial imaging by bone scan and CT scan (or MRI) of the abdomen and pelvis is strongly recommended, though systematic imaging surveillance is not mandatory in the absence of PSA rise or cancer-related symptoms 1
- In patients with CRPC on systemic treatment, regular imaging studies should be done to monitor disease response/progression 1
- Men on long-term ADT should be monitored for side-effects including osteoporosis (using bone densitometry) and metabolic syndrome 1
Important Considerations and Caveats
- PSA is not always a reliable indicator of disease activity in the rare population of patients with undifferentiated (or anaplastic) metastatic prostate cancer with neuroendocrine features 1
- Patients with evidence of neuro-endocrine change in their prostate cancer should receive chemotherapy in addition to ADT 1
- Docetaxel should not be administered to patients with neutrophil counts <1500 cells/mm³, and blood counts should be monitored frequently as neutropenia may be severe and result in infection 3
- ADT can produce multiple side effects including vasomotor flushing, sexual dysfunction, fatigue, cognitive impairment, reduced sleep quality, gynecomastia, and anemia, which can significantly decrease quality of life 4
- Hormonal therapy can also interfere with bone metabolism and induce metabolic and cardiovascular complications, requiring preventive measures and patient education 4