In a man with stage IV prostate cancer metastatic to the spine, what is the role of bilateral orchidectomy as androgen‑deprivation therapy?

Role of Bilateral Orchidectomy in Stage 4 Prostate Cancer with Spinal Metastases

Bilateral orchidectomy is a recommended first-line androgen deprivation therapy option for metastatic prostate cancer and remains equally effective as medical castration with LHRH agonists, offering rapid palliation, guaranteed compliance, and lower cost, though most patients prefer medical options due to psychological concerns. 1

Primary Treatment Recommendation

For stage IV prostate cancer with spinal metastases, bilateral orchidectomy or LHRH agonists are both recommended as initial palliative treatments, with equivalent efficacy. 1 The choice between surgical and medical castration should be determined through discussion with the patient, weighing the following factors:

Advantages of Bilateral Orchidectomy

• Rapid testosterone suppression: Serum testosterone falls to castrate levels (≤10 ng/mL) within days, providing quick symptom palliation 1
• Guaranteed compliance: Eliminates concerns about medication adherence 1
• Cost-effectiveness: One-time surgical procedure versus ongoing expensive injections 1
• Lower castrate testosterone levels: Achieves approximately 15 ng/dL compared to the historical 50 ng/dL threshold, which may improve disease control 2, 3
• Better quality of life outcomes: Recent data shows superior health-related quality of life scores compared to LHRH antagonists 2

Disadvantages of Bilateral Orchidectomy

• Irreversibility: Permanent procedure with no option for testosterone recovery 1
• Psychological impact: Significant emotional burden for many men, leading most to prefer medical castration when given the choice 1
• Surgical risks: Small risk of wound infection, hematoma, and pain 1

Clinical Efficacy Data

Historical VACURG data demonstrated that orchidectomy significantly reduced disease progression in stage IV patients (32% progression at 10 years versus 62% with placebo), though this did not translate to statistically significant improvements in overall survival (5-year OS: 32% versus 20% for placebo). 1 More recent studies confirm comparable time to progression between bilateral orchidectomy and medical castration (13.9 versus 13.8 months), with no significant survival differences. 4

Modern Treatment Context

While orchidectomy remains a valid option, current standard of care for metastatic prostate cancer involves ADT combined with additional agents (docetaxel, abiraterone, enzalutamide, or apalutamide), which provide proven survival benefits beyond castration alone. 5 Whether achieved surgically or medically, castration serves as the backbone therapy that must be maintained throughout the disease course, even when progression occurs. 6, 5

Long-Term Adverse Effects (Applicable to All Castration Methods)

Regardless of whether castration is achieved surgically or medically, patients will experience:

• Metabolic complications: Osteopenia, hypercholesterolemia, increased risk of diabetes and cardiovascular disease 1, 7, 8
• Physical symptoms: Vasoactive symptoms (hot flashes), weight gain, gynecomastia, fatigue 1, 9
• Cognitive and emotional changes: Mood lability, cognitive changes, loss of libido 1, 9
• Increased metabolic syndrome risk: Higher morbidity rates after 12 months of castrate testosterone levels 8

Combined Androgen Blockade Consideration

Adding a nonsteroidal antiandrogen to castration (combined androgen blockade) provides a small survival benefit (1-5% absolute mortality reduction at 5 years, NNT 20-100), but with increased toxicity. 1, 5 Patients willing to accept this trade-off should be offered nonsteroidal antiandrogen addition. 1

Practical Clinical Algorithm

For symptomatic stage IV disease with spinal metastases:

1. Initiate ADT immediately (either orchidectomy or LHRH agonist) 1
2. Add systemic intensification with docetaxel, abiraterone, enzalutamide, or apalutamide for survival benefit 5
3. Monitor testosterone levels every 3-4 weeks initially to confirm castrate levels (<20 ng/dL preferred) 5, 3
4. Continue castration indefinitely throughout disease course, even if progression occurs 6, 5
5. Implement bone protection given spinal metastases, though antiresorptive therapy benefit is limited in noncastrate bone metastases 5

Key Clinical Pitfalls to Avoid

• Do not discontinue castration (surgical or medical) even when disease progresses to castration-resistant state, as androgen receptor remains active and continued suppression is essential for subsequent therapies to work 6
• Do not use intermittent ADT in metastatic disease; continuous ADT is recommended 5
• Do not offer steroidal antiandrogens as monotherapy 1
• Do not delay systemic intensification in appropriate candidates, as ADT monotherapy is no longer optimal first-line treatment 5