Abiraterone for T3aN0M0 Prostate Cancer with Gleason 4+3
For your patient with T3aN0M0 prostate adenocarcinoma, Gleason 4+3, and high PSA, adding abiraterone to radiation plus ADT is recommended if the patient meets specific high-risk criteria, specifically having at least 2 of the following: T3-T4 stage, PSA >40 ng/mL, or Gleason score 8-10. 1, 2
Determining Eligibility for Abiraterone
Your patient has confirmed T3a disease and Gleason 4+3 (score 7), which counts as 1 high-risk feature. The critical decision point is whether the PSA level is >40 ng/mL:
If PSA >40 ng/mL: The patient meets criteria (2 of 3 high-risk features: T3 stage + PSA >40) and should receive abiraterone 1000 mg daily plus prednisone 5 mg daily for 24 months in combination with radiation therapy and ADT for 24-36 months 1, 2
If PSA ≤40 ng/mL: The patient has only 1 high-risk feature and does not meet the evidence-based criteria for abiraterone addition. Standard treatment would be radiation plus long-term ADT (24-36 months) alone 3, 1
Evidence Supporting This Approach
The STAMPEDE trial specifically included patients with high-risk N0M0 disease (defined as 2 of 3 factors: T3/4, PSA >40, or Gleason 8-10) and demonstrated significant survival benefit with abiraterone 3:
- Overall survival improved with hazard ratio 0.63 (95% CI 0.5-0.76, P<0.0001) 3
- Failure-free survival improved dramatically in the M0 subset (HR 0.21, P<0.0001) 3
- In non-metastatic disease, abiraterone was given for 2 years when combined with curative-intent radiation 3
The American Society of Clinical Oncology endorses this approach, showing metastasis-free survival of 82% vs 69% at 6 years and overall survival HR 0.60 when abiraterone is added to radiation plus ADT in appropriately selected high-risk patients 2
Critical Exclusion Criteria
Abiraterone should NOT be added if:
- The patient is not receiving definitive radiation therapy—the evidence specifically requires radiotherapy as part of the treatment plan 2
- The patient has only 1 high-risk feature (in your case, if PSA ≤40 ng/mL) 1, 2
- The patient is ≥70 years old with significant comorbidities, as older patients experienced attenuated survival benefits (HR 0.94 vs 0.51 in younger patients) and increased grade 3-5 adverse events (47% vs 33%) 3, 2
Practical Implementation
If abiraterone is indicated:
- Dosing: Abiraterone acetate 1000 mg once daily on an empty stomach (at least 1 hour before or 2 hours after food) plus prednisone 5 mg once daily for 24 months 3, 2, 4
- Duration: Continue for 2 years in combination with radiation and ADT (which continues for 24-36 months total) 3
- Mandatory monitoring: Baseline and ongoing assessment of blood pressure, serum potassium, liver function tests, and cardiac evaluation 3, 5
Expected Adverse Events to Monitor
- Mineralocorticoid excess effects: hypertension (21% grade 3-4), hypokalemia (12% grade 3-4), and edema 3, 2
- Hepatotoxicity requiring regular liver function monitoring (7% grade 3-5) 3
- Cardiac disorders including atrial fibrillation (rare but increased) 3
- Overall discontinuation rate due to adverse events is approximately 12% 3
Common Pitfall to Avoid
Do not use abiraterone in T3N0M0 disease without confirming the patient meets the 2-of-3 high-risk criteria and is receiving definitive radiation therapy. The LATITUDE trial studied metastatic disease with different criteria (Gleason 8-10, ≥3 bone metastases, visceral metastases), which does not apply to your non-metastatic patient 3, 2. The STAMPEDE non-metastatic cohort provides the relevant evidence base for your clinical scenario 3.