In a 68-year-old man with rapidly rising PSA indicating aggressive prostate cancer, what is androgen-deprivation therapy (ADT) and what is abiraterone acetate, and how do they work against prostate cancer?

What is ADT Therapy and Abiraterone? How Do They Work Against Prostate Cancer?

ADT (androgen-deprivation therapy) is the foundational treatment that lowers testosterone levels to starve prostate cancer cells, while abiraterone is a more potent hormonal agent that blocks testosterone production from all sources (testes, adrenal glands, and within the tumor itself) by inhibiting the CYP17 enzyme—and when combined, they significantly improve survival in aggressive metastatic prostate cancer. 1, 2, 3

Understanding ADT (Androgen-Deprivation Therapy)

ADT works by reducing testosterone to castrate levels (below 50 ng/dL), which is critical because prostate cancer cells depend on androgens (male hormones) to grow and survive. 4

How ADT is delivered:

• LHRH agonists (like leuprolide, goserelin): Initially stimulate then suppress testosterone production from the testes
• LHRH antagonists (like degarelix): Directly and immediately block testosterone without initial flare
• Surgical castration (orchiectomy): Permanent removal of testes
• Antiandrogens (like bicalutamide): Block androgen receptors from being activated 4

Important caveat: LHRH agonists cause an initial testosterone "flare" in the first 7 days, which can worsen bone pain or urinary symptoms in men with extensive bone metastases. This requires co-administration of an antiandrogen for at least 7 days to prevent complications. LHRH antagonists avoid this problem entirely. 2

Understanding Abiraterone Acetate

Abiraterone is a CYP17 inhibitor that represents a more complete androgen blockade than traditional ADT alone. 3, 5

Mechanism of action:

• Irreversibly blocks CYP17A1 enzyme, which is essential for converting precursor molecules into testosterone
• Eliminates testosterone production from three sources: testes (already suppressed by ADT), adrenal glands, and the tumor microenvironment itself
• Reduces testosterone to undetectable levels, far below what ADT alone achieves 5, 6, 7

Critical administration details from FDA labeling:

• Dose: 1,000 mg once daily taken with prednisone 5 mg twice daily
• Must be taken on empty stomach: No food 2 hours before and 1 hour after taking the medication
• Taking with food dramatically increases drug absorption and side effects 3
• Prednisone is mandatory to prevent mineralocorticoid excess (high blood pressure, low potassium, fluid retention) 3

How They Work Together Against Prostate Cancer

For your 68-year-old patient with rapidly rising PSA indicating aggressive disease, the combination of ADT plus abiraterone provides superior survival compared to ADT alone. 1, 2

Evidence from major trials:

• LATITUDE trial: In high-risk metastatic disease (defined as ≥2 of: Gleason 8-10, ≥3 bone metastases, or visceral metastases), ADT plus abiraterone reduced death risk by 38% (HR 0.62) with median survival improving from 36.5 to 53.3 months 1, 2, 8
• STAMPEDE trial: Similar 37% reduction in death risk (HR 0.63) across broader metastatic population 1

Practical treatment algorithm for metastatic castration-sensitive prostate cancer:

1. High-risk or high-volume disease (extensive bone metastases, visceral metastases, Gleason 8-10): Strongly recommend ADT + abiraterone 1, 9

2. Low-volume disease: ADT + abiraterone is still beneficial but with moderate strength recommendation 9

3. Alternative option: ADT + docetaxel chemotherapy (6 cycles), particularly for high-volume disease, though this has not been directly compared to abiraterone 1

Key Side Effects to Monitor

Abiraterone-specific toxicities (related to mineralocorticoid excess):

• Hypertension (most common)
• Hypokalemia (low potassium)
• Fluid retention/edema
• Liver enzyme elevations
• Cardiac events (atrial fibrillation, though rare)
• Fatigue and hot flashes 2, 3

These are generally manageable with dose adjustments of prednisone, addition of mineralocorticoid antagonists (eplerenone), or potassium supplementation. Only 12% of patients discontinue due to side effects. 2

ADT-related toxicities:

• Hot flashes
• Sexual dysfunction
• Osteoporosis/fracture risk
• Metabolic syndrome (weight gain, diabetes risk)
• Cardiovascular events
• Cognitive changes 4

Critical Clinical Pearls

For patients with diabetes: Monitor glucose levels closely as both ADT and corticosteroids (prednisone) can worsen glycemic control 3

Contraception requirement: Males with female partners of childbearing potential must use effective contraception during treatment and for 3 weeks after stopping abiraterone, as it causes fetal harm 3

Do not combine with radium-223: This combination showed increased mortality and fracture rates 3

PSA monitoring: Achieving PSA ≤0.2 ng/mL (ideally ≤0.02 ng/mL) predicts better long-term outcomes and delayed progression 10, 11

Sequential therapy note: If disease progresses on ADT + abiraterone, switching to another androgen receptor pathway inhibitor (like enzalutamide) shows diminished response rates. Chemotherapy (cabazitaxel) may be more effective at that point. 12