Criteria for Abiraterone in High-Risk Locally Advanced Prostate Cancer
Abiraterone acetate (1000 mg daily) combined with prednisone (5 mg daily) and ADT should be offered to patients with high-risk locally advanced non-metastatic prostate cancer who are receiving radiotherapy, based on strong evidence demonstrating improved metastasis-free survival (82% vs 69% at 6 years) and overall survival (HR 0.60). 1, 2, 3
Specific Eligibility Criteria
Disease Characteristics Required
- Node-positive disease (cN1), OR 2, 3
- Node-negative disease with at least 2 of the following high-risk features: 3
Treatment Context Requirements
- Radiotherapy must be planned or delivered - this is the critical distinguishing factor for locally advanced disease 1, 2, 3
- Whole-pelvic radiation therapy is recommended for node-positive patients 2
- Standard EBRT dosing is 74 Gy in 37 fractions or equivalent hypofractionated schedules 3
Treatment Duration
- Abiraterone acetate: 2 years 2, 3
- ADT: 3 years total 2, 3
- Prednisone: 5 mg daily throughout abiraterone treatment 4, 5
Evidence Strength and Quality
The recommendation is based on pooled analysis from STAMPEDE trials showing: 3
- Metastasis-free survival: 82% vs 69% at 6 years (HR 0.53, p<0.0001) 3
- Overall survival: HR 0.60 (95% CI 0.48-0.73, p<0.0001) 3
- Prostate cancer-specific survival: HR 0.49 (95% CI 0.37-0.65, p<0.0001) 3
ASCO guidelines specifically recommend this combination for men with noncastrate locally advanced nonmetastatic prostate cancer who have undergone radiotherapy, rather than castration monotherapy alone. 1
Critical Exclusions and Contraindications
Do NOT offer abiraterone in the following scenarios:
- Patients with locally advanced disease who are not receiving radiotherapy - the evidence specifically requires radiotherapy as part of the treatment plan 1, 3
- Patients who have already progressed to castration-resistant disease (different indication) 1
- Patients unable to tolerate corticosteroid co-administration 4
Mandatory Monitoring Requirements
Monthly monitoring during initial treatment phase: 2, 4
- Blood pressure (hypertension occurs in 21% grade 3-4) 2
- Serum potassium (hypokalemia in 12% grade 3-4) 2
- Liver function tests (hepatotoxicity risk) 2
- Symptom-directed cardiac assessment 2
Age-Related Considerations
Patients ≥70 years experience increased toxicities (47% vs 33% grade 3-5 adverse events) and may have attenuated survival benefits, requiring careful risk-benefit assessment. 2
Common Pitfalls to Avoid
- Never use abiraterone without concurrent prednisone - this prevents mineralocorticoid excess syndrome (hypertension, hypokalemia, edema) that occurs due to CYP17A1 inhibition 4
- Do not confuse with metastatic disease criteria - the LATITUDE high-risk definition (≥2 of: Gleason ≥8, ≥3 bone lesions, visceral disease) applies to metastatic disease, not locally advanced 1, 5
- Radiotherapy is non-negotiable - without planned radiotherapy, this indication does not apply 1, 3