What is the recommended approach for Androgen Deprivation Therapy (ADT) in patients with prostate cancer?

Recommended Approach for Androgen Deprivation Therapy (ADT) in Prostate Cancer

ADT should be tailored based on disease stage, with continuous ADT recommended as first-line treatment for metastatic hormone-naïve disease, while intermittent ADT is preferred for biochemical relapse after radiation therapy to improve quality of life while maintaining efficacy. 1

ADT Indications by Disease Stage

Localized/Locally Advanced Disease

• Primary ADT alone is NOT recommended as standard initial treatment for non-metastatic disease 1
• For high-risk or locally advanced prostate cancer:
  • External beam radiotherapy plus hormone treatment is recommended (Level I, B) 1
  • Neoadjuvant and concurrent ADT for 4-6 months is recommended for men receiving radical RT for high-risk disease 1
  • Adjuvant ADT for 2-3 years is recommended for men receiving neoadjuvant hormonal therapy and radical RT who are at high risk of prostate cancer mortality 1
  • Consider for intermediate-risk disease 1

Biochemical Recurrence

• Early ADT is not routinely recommended for men with biochemical relapse unless they have:
  • Symptomatic local disease
  • Proven metastases
  • PSA doubling time <3 months 1
• Intermittent ADT is recommended for men with biochemical relapse after radical RT 1
  • Provides improved quality of life during off-treatment periods 1
  • Similar overall survival compared to continuous ADT 1, 2

Metastatic Disease

• Continuous ADT is recommended as first-line treatment for metastatic hormone-naïve disease 1, 2
• ADT plus docetaxel is recommended for metastatic hormone-naïve disease in men fit enough for chemotherapy 1

ADT Approaches and Options

Primary ADT Methods

1. Surgical castration (bilateral orchiectomy)

   • Provides rapid testosterone reduction
   • Permanent effect
   • Lower risk of fractures and cardiovascular complications 2

2. Medical castration

   • LHRH agonists (leuprolide, goserelin)
   • LHRH antagonists (degarelix)
   • Equally effective as surgical castration 1, 2

Optimal ADT Approach

• LHRH agonists and bilateral orchiectomy are equally effective 1, 2
• Combined androgen blockade (medical or surgical castration plus antiandrogen) provides no proven benefit over castration alone in metastatic disease 1
• Antiandrogen therapy should precede or be co-administered with LHRH agonist for at least 7 days in patients with overt metastases at risk of flare symptoms 1
• Antiandrogen monotherapy is less effective than medical or surgical castration and not recommended 1

LHRH Antagonists vs. Agonists

• LHRH antagonists (e.g., degarelix) provide:
  • Direct and immediate blockade of pituitary LHRH receptors
  • More rapid testosterone suppression without initial surge or microsurges
  • Better control of FSH and PSA
  • Potentially prolonged delay to progression 3

Monitoring and Management

Testosterone Monitoring

• Adequate suppression of serum testosterone to <50 ng/dL is essential 2
• Regular monitoring of testosterone levels is necessary to avoid inadequate suppression 2, 4
• Consider testosterone-based dosing intervals rather than fixed schedules 4

Exercise Recommendation

• Men starting ADT should be informed that regular exercise reduces fatigue and improves quality of life 1

Side Effects and Complications

Common Side Effects

• Sexual dysfunction and decreased libido
• Hot flashes
• Fatigue
• Metabolic changes (weight gain, insulin resistance)
• Bone loss and increased fracture risk
• Cardiovascular complications
• Cognitive changes 2, 5

Risk Mitigation

• Cardiovascular risk assessment before initiating ADT
• Bone health monitoring and preventive measures
• Screening for and intervention to prevent/treat diabetes and cardiovascular disease 1, 2
• Supplemental calcium (1200 mg daily) and vitamin D3 (800-1000 IU daily) for all men older than 50 years 1
• Consider zoledronic acid (4 mg IV annually) or alendronate (70 mg PO weekly) when fracture risk warrants 1

Special Considerations

Castration-Resistant Prostate Cancer (CRPC)

• Continue ADT as the androgen receptor remains active 1
• Secondary hormonal therapies for CRPC:
  • Abiraterone or enzalutamide for asymptomatic/mildly symptomatic men with chemotherapy-naïve metastatic CRPC 1
  • Radium-223 for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases 1
  • Docetaxel for men with metastatic CRPC 1

Pitfalls to Avoid

1. Using primary ADT alone for non-metastatic disease
2. Failing to monitor testosterone levels during treatment
3. Not addressing side effects and complications of ADT
4. Overlooking the potential benefits of intermittent ADT for appropriate patients
5. Switching between LHRH analogues after PSA progression (shown to be ineffective) 6

By following these evidence-based recommendations, clinicians can optimize ADT use in prostate cancer management while minimizing adverse effects and maintaining quality of life.