What is the recommended androgen deprivation therapy (ADT) regimen for an adult male with advanced or metastatic prostate cancer, including drug choice, dosing, monitoring, and bone health management?

Androgen Deprivation Therapy for Advanced/Metastatic Prostate Cancer

Primary Recommendation

For metastatic castration-sensitive prostate cancer, ADT alone is no longer the standard of care—treatment intensification with ADT plus docetaxel, abiraterone, enzalutamide, or apalutamide represents four separate standards of care, with triplet therapy (ADT + docetaxel + novel androgen receptor inhibitor) preferred for fit patients. 1, 2

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ADT Backbone Selection

Standard ADT Options (Choose One)

• LHRH agonists (leuprolide, goserelin, triptorelin) administered as depot injections every 1-6 months depending on formulation 3, 2

  • Critical: Require concurrent antiandrogen coverage (bicalutamide 50 mg daily) for 3-4 weeks to prevent testosterone flare 3, 2

• LHRH antagonists (degarelix 240 mg loading dose, then 80 mg monthly; or relugolix 360 mg loading, then 120 mg daily) 3, 2

  • Advantage: No testosterone flare, no antiandrogen coverage needed 3, 2

• Bilateral orchiectomy (surgical castration) 3, 2

  • Advantage: Lower risk of fracture, peripheral arterial disease, and cardiac complications compared to LHRH agonists; most cost-effective option 3
  • Disadvantage: Irreversible, psychological impact

Do NOT Use

• Bicalutamide monotherapy is not supported as adjuvant therapy after primary treatment 3
• Combined androgen blockade (LHRH agonist + antiandrogen continuously) provides only 3-5% overall survival advantage and is not routinely recommended except in high-volume metastatic disease 3, 2

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Treatment Intensification for Metastatic Disease

For Fit Patients (ECOG 0-1, No Significant Comorbidities)

Triplet therapy is preferred: 2

1. ADT (any modality above) +
2. Docetaxel 75 mg/m² IV every 3 weeks for 6 cycles +
3. Darolutamide 600 mg PO twice daily OR Abiraterone 1000 mg PO daily + prednisone 5 mg PO twice daily

Evidence: 4-year overall survival 62.7% vs 50.4% with ADT alone (HR 0.68, P<0.001) 2

For Patients Unfit for Chemotherapy

ADT doublet therapy (choose one): 1

• ADT + Abiraterone 1000 mg PO daily + prednisone 5 mg PO twice daily
• ADT + Enzalutamide 160 mg PO daily
• ADT + Apalutamide 240 mg PO daily

All four options (including ADT + docetaxel) represent separate standards of care with no established superiority of one over another 1

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Castration Target and Monitoring

Testosterone Monitoring

• Target: Maintain serum testosterone <50 ng/dL (<1.7 nmol/L) continuously 1, 3, 2
• Optimal target: <20 ng/dL (<0.7 nmol/L) associated with improved outcomes 4
• Frequency: Confirm castrate levels at 3 months, then every 6-12 months 2

PSA Monitoring

• Frequency: Every 3-6 months 2
• For intermittent ADT consideration: PSA must decline to ≤4 ng/mL after 7 months of induction therapy 3

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Bone Health Management

Bone-Modifying Agents (Mandatory for Bone Metastases)

Choose one: 1, 2

• Denosumab 120 mg subcutaneously every 4 weeks
• Zoledronic acid 4 mg IV every 3-4 weeks

Baseline and Monitoring

• Baseline bone densitometry (DEXA scan) before initiating ADT 2
• Calcium 1200 mg daily + Vitamin D 800-1000 IU daily for all patients on ADT 2
• Monitor: Serum calcium, creatinine, dental health (risk of osteonecrosis of jaw) 2

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Intermittent vs. Continuous ADT

Continuous ADT is Standard

• Continuous ADT is superior for metastatic disease: Median survival 5.8 years vs 5.1 years with intermittent ADT (HR 1.10) 3
• Never use intermittent ADT in minimal disease burden: Post-hoc analysis shows worse outcomes (5.4 vs 6.9 years, HR 1.19) 3

Intermittent ADT May Be Considered Only For:

• High-risk biochemically recurrent nonmetastatic disease after radical prostatectomy or radiation therapy 1, 3
• Protocol if used: 7-month induction until PSA ≤4 ng/mL, restart when PSA reaches 20 ng/mL 3

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Castration-Resistant Disease Management

When CRPC Develops (PSA/radiographic progression despite testosterone <50 ng/dL)

Continue ADT backbone indefinitely and add sequential therapies: 1

1. First-line CRPC: Abiraterone + prednisone OR enzalutamide (if not used in hormone-sensitive setting) 1
2. Second-line CRPC: Docetaxel 75 mg/m² every 3 weeks (if not used earlier) 1
3. Third-line CRPC: Cabazitaxel 25 mg/m² every 3 weeks with mandatory G-CSF OR Lutetium-177 PSMA-617 (if PSMA-positive on imaging) 1, 5
4. Bone-predominant CRPC: Radium-223 50 kBq/kg IV every 4 weeks for 6 cycles 1

Do not repeat failed therapies except docetaxel rechallenge after novel hormone therapy progression 1

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Cardiovascular and Metabolic Monitoring

Baseline Assessment

• Cardiovascular risk factors: Blood pressure, lipid panel, fasting glucose, HbA1c 2
• Baseline ECG if using LHRH agonists (QT prolongation risk) 2

Ongoing Monitoring

• Every 3-6 months: Blood pressure, weight, fasting glucose, lipid panel 2
• Screen for: Hot flashes, fatigue, erectile dysfunction, gynecomastia, osteoporosis, metabolic syndrome 2

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Critical Pitfalls to Avoid

• Never use ADT monotherapy as primary treatment for early-stage, low-risk disease—no 15-year survival benefit vs observation 3
• Never initiate LHRH agonists without antiandrogen coverage—risk of testosterone flare and disease progression 3, 2
• Never discontinue ADT backbone when progressing to CRPC—continue indefinitely with sequential therapy additions 1, 4
• Never assume intermittent ADT is equivalent to continuous ADT in metastatic disease—survival data favor continuous therapy 3
• Never use treatment intensification in low-volume, asymptomatic disease without shared decision-making—toxicity must be balanced against benefit 1