Dose Prescription in Low Volume Metastatic Prostate Cancer
For patients with low-volume metastatic castration-naïve prostate cancer, ADT alone (without docetaxel) is the recommended approach, using standard castration dosing with LHRH agonists, LHRH antagonists, or bilateral orchiectomy, with consideration for adding abiraterone 1000 mg daily plus prednisone 5 mg daily based on STAMPEDE data. 1
ADT Dosing Options for Low-Volume Disease
The standard ADT regimens for metastatic castration-naïve prostate cancer include 1:
- LHRH agonist alone (leuprolide, goserelin, or similar agents at standard dosing intervals)
- LHRH antagonist (degarelix 240 mg loading dose, then 80 mg monthly; or relugolix 360 mg loading dose, then 120 mg daily)
- Bilateral orchiectomy (surgical castration)
Target testosterone suppression: <50 ng/dL 1
Critical Distinction: Docetaxel Should NOT Be Added in Low-Volume Disease
Docetaxel plus ADT should not be offered to patients with low-volume metastatic disease 1. This is a strong recommendation based on high-quality evidence from CHAARTED and GETUG-AFU-15 trials showing no overall survival benefit for low-volume disease, regardless of whether metastases were present at diagnosis or developed after local therapy failure 1.
Low-volume disease is defined as fewer than 4 bone metastases with none outside the spine/pelvis AND no visceral metastases 1.
Intensification Options for Low-Volume Disease
Abiraterone Addition (Moderate Recommendation)
For low-risk de novo metastatic noncastrate prostate cancer, ADT plus abiraterone may be offered per STAMPEDE 1. The dosing is:
- Abiraterone acetate 1000 mg orally once daily
- Prednisone 5 mg orally once daily
- Continue until progression 1
The STAMPEDE trial included patients with low-volume disease and demonstrated overall survival benefits, though the evidence is stronger for high-risk disease 1.
Alternative Intensification Agents
Three additional agents represent separate standards of care when combined with ADT 1:
- Enzalutamide 160 mg orally once daily 2
- Apalutamide (dosing per FDA approval)
- Docetaxel (contraindicated in low-volume disease) 1
No evidence exists to guide sequencing or combination of these agents 1.
Important Caveats for LHRH Agonist Use
In patients with weight-bearing bone metastases at risk for testosterone flare symptoms:
- Antiandrogen therapy must precede or be coadministered with LHRH agonist for at least 7 days 1
- This prevents ligand binding to androgen receptors during the initial testosterone surge
- LHRH antagonists do not require antiandrogen coadministration as they cause no initial flare 1
Monitoring Target
PSA ≤4 ng/mL after 7 months of ADT is associated with improved survival in newly diagnosed metastatic prostate cancer 1.
Radiation Therapy Consideration
For low-volume metastatic disease, consider adding external beam radiation therapy (EBRT) to the primary tumor in addition to systemic ADT 1. This approach is discussed in NCCN guidelines as a potential survival benefit, though specific dosing recommendations for radiation are addressed separately.