When should abiraterone be initiated together with androgen-deprivation therapy in patients with very high‑risk prostate cancer?

When to Start Abiraterone with ADT in Very High-Risk Prostate Cancer

Abiraterone should be initiated immediately at the time of starting ADT in patients with newly diagnosed very high-risk prostate cancer, particularly those with metastatic disease or high-risk features meeting LATITUDE criteria (Gleason 8-10, ≥3 bone metastases, or visceral metastases). 1

Treatment Initiation Criteria

Start abiraterone plus ADT upfront (not delayed) in patients with:

• Metastatic castration-sensitive prostate cancer (mCSPC) - Category 1 recommendation 1
• High-risk features defined as ≥2 of the following 1:
  • Gleason score 8-10
  • ≥3 bone metastases
  • Visceral metastases
• Node-positive (N1) disease - even without distant metastases 1
• High-volume metastatic disease 1

The evidence strongly supports starting abiraterone at diagnosis rather than waiting for castration resistance. In the STAMPEDE trial, 95% of patients had newly diagnosed disease, and immediate abiraterone use showed superior outcomes compared to deferring therapy until the castration-resistant setting 1. This is critical: 58% of control patients eventually received subsequent life-prolonging therapy (22% abiraterone, 26% enzalutamide), yet upfront use still demonstrated significant survival advantage (HR 0.63, P<0.0001) 1.

Dosing Regimen

Standard dosing 1, 2:

• Abiraterone 1,000 mg once daily (on empty stomach, 1 hour before or 2 hours after meals)
• Prednisone 5 mg once daily (NOT twice daily as in mCRPC)
• Continue concurrent ADT (GnRH analog or bilateral orchiectomy)

Alternative cost-saving option 1:

• Abiraterone 250 mg daily after a low-fat breakfast (instead of 1,000 mg fasted)
• May reduce financial toxicity and improve adherence

Duration of Treatment

Treatment duration depends on disease extent 1:

• M1 (metastatic) disease: Continue until progression
• N1 or M0 disease with curative-intent radiation: 2 years of abiraterone if external beam radiation therapy (EBRT) is used

Age Considerations - Important Caveat

Exercise caution in patients ≥70 years old. The survival benefit was substantially smaller in older patients (HR 0.94 vs HR 0.51 in those <70 years), and they experienced significantly higher toxicities with increased grade 3-5 adverse events (47% vs 33%) and treatment-related deaths (9 vs 3) 1. This represents genuine heterogeneity in clinical benefit by age and comorbidity that must factor into decision-making.

Monitoring Requirements

Before and during treatment 2:

• Liver function: ALT, AST, bilirubin
  • Every 2 weeks for first 3 months
  • Then monthly thereafter
• Blood pressure and potassium: At least monthly 2
• Cardiovascular monitoring: Especially in patients with pre-existing cardiac disease 2
• Blood glucose: In diabetic patients, particularly those on thiazolidinediones or repaglinide 2

Clinical Outcomes Supporting Immediate Use

The LATITUDE trial demonstrated in high-risk mCSPC 1:

• Median OS: 53.3 vs 36.5 months (HR 0.66, P<0.0001)
• 3-year OS: 66% vs 49%
• Delayed castration-resistant progression: 33.2 vs 14.8 months
• Improved patient-reported outcomes including pain, fatigue, and quality of life

The failure-free survival benefit was consistent across all subgroups: M1 (HR 0.31), N1 (HR 0.29), and M0 (HR 0.21) disease 1.

Common Pitfall to Avoid

Do not wait for castration resistance to develop before adding abiraterone. The evidence unequivocally shows that upfront combination therapy provides superior outcomes compared to sequential therapy. ADT monotherapy is strongly discouraged in metastatic castration-sensitive disease unless clear contraindications to combination therapy exist 1.

Do not combine abiraterone with radium Ra-223 - this combination showed increased fractures (28.6% vs 11.4%) and mortality (38.5% vs 35.5%) in the ERA-223 trial 2.