What hormone treatment is used to slow prostate cancer progression in adult males?

Hormone Treatment for Prostate Cancer

Androgen deprivation therapy (ADT) through either bilateral orchiectomy (surgical castration) or LHRH agonists (medical castration) is the standard hormone treatment used to slow prostate cancer progression. 1, 2

Standard First-Line ADT Options

Bilateral orchiectomy and LHRH agonists are equally effective and represent the two primary methods of achieving testosterone suppression in metastatic or advanced prostate cancer. 1, 2 Both approaches achieve castrate levels of testosterone (below 50 ng/dL), which correlates with improved disease control. 1, 3

LHRH Agonists (Medical Castration)

• LHRH agonists such as goserelin (Zoladex) and leuprolide provide reversible testosterone suppression and are the most commonly used medical approach. 4
• Critical caveat: LHRH agonists cause an initial testosterone surge ("flare") that can worsen symptoms, so an antiandrogen must be given concurrently for at least 7 days (some guidelines recommend 3-4 weeks) when starting therapy, particularly in patients with metastatic disease at risk of complications. 1, 2
• Goserelin achieves 94% PSA suppression at three months and provides sustained testosterone reduction. 4

Surgical Castration

• Bilateral orchiectomy provides immediate, permanent testosterone suppression without the risk of testosterone flare and is the most cost-effective option. 3
• This approach is particularly relevant in developing countries due to cost considerations and eliminates compliance issues associated with ongoing injections. 3

Enhanced Treatment: Combined Androgen Blockade

For patients willing to accept increased toxicity for a modest survival benefit, combined androgen blockade (CAB)—medical or surgical castration plus a nonsteroidal antiandrogen—should be offered. 1, 2

• CAB provides a 3-5% overall survival advantage compared to castration alone, particularly in patients with high-volume metastatic disease. 3
• The antiandrogen component blocks residual androgens from adrenal sources that castration alone does not eliminate. 5
• Common pitfall: Antiandrogen monotherapy (without castration) is less effective than castration and should not be recommended as primary treatment. 1

Specific Antiandrogens Used

Nonsteroidal antiandrogens such as flutamide, bicalutamide, and nilutamide are used in combination with castration therapy. 1, 6

• Flutamide is administered at 250 mg three times daily in combination with LHRH agonists to achieve "total androgen blockade." 6
• Important safety warning: Flutamide carries a risk of severe liver injury, particularly in the first 3 months of therapy, requiring monthly liver function monitoring for the first 4 months, then periodically thereafter. 6
• Steroidal antiandrogens should not be offered as monotherapy. 1

Treatment Duration and Timing

Continuous ADT is recommended over intermittent ADT for metastatic hormone-naïve prostate cancer based on evidence showing potential survival disadvantage with intermittent therapy. 2, 3

• For high-risk localized disease treated with radiation, neoadjuvant LHRH agonist therapy for 4-6 months is recommended, followed by adjuvant hormonal therapy for 2-3 years. 1
• Early ADT confers a small but statistically significant survival advantage and significant improvements in progression-free survival compared to deferred therapy. 1

Newer Agents for Castration-Resistant Disease

When cancer progresses despite castration (castration-resistant prostate cancer), castrate testosterone levels should be maintained while adding additional therapies. 1, 3

• Abiraterone (1000 mg daily) plus low-dose prednisone (5 mg twice daily) is a category 1 recommendation for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer, blocking adrenal androgen synthesis. 1
• Enzalutamide (160 mg daily) is another option that blocks androgen receptor activation more potently than first-generation antiandrogens. 1

Critical Monitoring Requirements

• Verify achievement and maintenance of castrate testosterone levels (<50 ng/dL) throughout treatment. 1, 3
• Monitor for ADT-related adverse effects including bone loss, metabolic changes, cardiovascular complications, and sexual dysfunction. 1, 7
• Bone density screening is essential for patients on long-term ADT due to increased fracture risk. 7