What is the recommended hormonal therapy for prostate cancer?

Hormonal Therapy for Prostate Cancer

For metastatic prostate cancer, the recommended first-line hormonal therapy is androgen suppression using bilateral orchiectomy or an LHRH agonist/antagonist alone, without routine addition of anti-androgens. 1

First-Line Hormonal Therapy Options

Surgical vs. Medical Castration

• Bilateral orchiectomy and LHRH agonists are equally effective as initial palliative treatments for metastatic prostate cancer 1
• Orchiectomy is simple, cost-effective, and provides immediate testosterone reduction, but is irreversible and may cause psychological distress to patients 1
• LHRH agonists (such as goserelin) are equally effective, available in depot injections, potentially reversible, but more expensive 1, 2
• LHRH antagonists offer equivalent testosterone reduction without the initial testosterone surge seen with LHRH agonists, eliminating the need for anti-androgen coverage during initiation 1, 3

Recommended Administration

• When starting LHRH agonists, a short-course anti-androgen should be used to prevent disease flare due to initial testosterone surge 1
• Goserelin has demonstrated long-term survival benefits in patients with localized and locally advanced prostate cancer 2
• Goserelin is available in both 3.6 mg (monthly) and 10.8 mg (every 12 weeks) formulations with similar testosterone suppression and PSA response 4

Combined Androgen Blockade (CAB)

• Combined androgen blockade (adding an anti-androgen to surgical or medical castration) is not recommended for routine first-line treatment 1
• Meta-analyses show only a minimal survival benefit with CAB (5-year survival of 25.4% with CAB vs. 23.6% for androgen deprivation alone) 1
• The small potential benefit must be weighed against increased side effects and costs 1
• If considering CAB, nonsteroidal anti-androgens are preferred over steroidal anti-androgens 1

Anti-Androgen Monotherapy

• Nonsteroidal anti-androgens (flutamide, nilutamide, bicalutamide) as monotherapy show equivalent survival to castration in some studies, but with different side effect profiles 1
• Bicalutamide has a more convenient once-daily dosing compared to flutamide (three times daily) 5
• Steroidal anti-androgens are not recommended as monotherapy 1
• Pure anti-androgens are associated with poorer outcomes compared to watchful waiting for stage T1b-T2b disease and are not recommended in this setting 1

Special Considerations

Cardiovascular Risk Management

• Patients should undergo comprehensive cardiovascular risk assessment before starting ADT, especially those over 65 with pre-existing cardiovascular conditions 6
• Regular monitoring of lipid profiles and glucose metabolism is recommended for patients on ADT 6
• Regular physical exercise can help reduce fatigue and improve quality of life in patients on LHRH agonists 6

Second-Line Hormonal Therapy

• For castration-resistant prostate cancer (CRPC), patients should continue androgen suppression and be considered for additional hormonal therapies 1
• Newer agents for CRPC include abiraterone acetate and enzalutamide 1
• Enzalutamide has shown superior progression-free survival compared to bicalutamide in CRPC (15.7 vs. 5.8 months) 7

Hormonal Therapy with Radiation

• For high-risk localized disease, androgen deprivation therapy should be given before, during, and after radiotherapy for a minimum of 6 months 1
• For patients at high risk for recurrence (T3a or Gleason score 8-10 or PSA > 20 ng/ml), androgen deprivation therapy for at least 2 years with 3D radiation therapy is recommended 1
• Neoadjuvant or adjuvant hormone therapy should be included in the protocol for high-risk patients with localized prostatic tumors 1

Common Pitfalls and Caveats

• Diethylstilbestrol (DES) is not recommended as standard first-line treatment due to significant cardiovascular and thrombotic risks 1
• Patients receiving long-term bicalutamide monotherapy should be given breast bud irradiation (8-10 Gy in one fraction) to prevent painful gynecomastia 1
• Intermittent androgen deprivation (IAD) has not been established as non-inferior to continuous therapy for metastatic disease, with one large trial showing median survival of 5.8 years on continuous AD versus 5.1 years with IAD 1
• Periodic monitoring of serum testosterone levels should be considered if the anticipated clinical or biochemical response to treatment has not been achieved 4