Definition
- Systemic therapy to reduce circulating testosterone to castrate levels (<50 ng/dL) to suppress androgen‐driven prostate cancer growth.
- Standard backbone for hormone‐sensitive and castration‐resistant prostate cancer (continued in mCRPC).
Rationale
- Prostate cancer cells rely on androgen receptor (AR) signaling for growth.
- Lowering androgen levels slows tumor proliferation and delays disease progression.
Methods of ADT
| Approach | Agents / Methods | Key Points |
|---|---|---|
| Surgical castration | Bilateral orchiectomy | Immediate testosterone drop; irreversible; no compliance issue. |
| Medical castration – LHRH agonists | Leuprolide, goserelin, triptorelin | Initial testosterone flare (↑ symptoms risk: bone pain, spinal cord compression); combine with antiandrogen for 2–4 weeks at start. |
| Medical castration – LHRH antagonists | Degarelix (SC), relugolix (oral) | No flare; rapid testosterone suppression. |
| Antiandrogens (nonsteroidal) | Bicalutamide, flutamide, nilutamide | Used short‐term to block flare or combined androgen blockade; not for monotherapy long‐term. |
| Androgen synthesis inhibitors | Abiraterone + prednisone | Inhibits CYP17 → blocks adrenal/testicular androgen production; requires steroids to prevent mineralocorticoid excess. |
Administration & Dosing Examples
- Leuprolide: 7.5 mg IM monthly, 22.5 mg q3mo, 45 mg q6mo.
- Goserelin: 3.6 mg SC monthly, 10.8 mg q3mo.
- Degarelix: 240 mg SC loading dose (two injections), then 80 mg monthly.
- Relugolix: 360 mg PO loading, then 120 mg daily.
Adverse Effects & Monitoring
- Common: Hot flashes, sexual dysfunction, fatigue, gynecomastia.
- Metabolic: Weight gain, insulin resistance, dyslipidemia.
- Skeletal: Osteoporosis, fracture risk.
- CV risk: Possible ↑ risk of MI, stroke (more with agonists).
- Others: Mood changes, anemia, muscle loss.
Monitoring:
- Testosterone, PSA every 3–6 months.
- Fasting glucose, lipid profile, HbA1c periodically.
- Bone mineral density (DEXA) every 1–2 years.
- Monitor for cardiovascular risk factors.
Pharmacist Role
- Ensure testosterone <50 ng/dL is maintained.
- Manage flare prevention with antiandrogen lead‐in for LHRH agonists.
- Counsel on lifestyle measures (exercise, calcium/vitamin D, smoking cessation).
- Recommend bone‐protective therapy (zoledronic acid or denosumab) if fracture risk high.
- Screen for and manage metabolic and cardiovascular effects.
Key Takeaway:
ADT is the foundation of prostate cancer management at all stages; method selection depends on urgency of testosterone suppression, patient comorbidities, and preferences. Pharmacists play a critical role in monitoring efficacy, preventing complications, and optimizing supportive care.