What are the key findings of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) non-metastatic trial for a patient with high-risk non-metastatic prostate cancer, specifically T3aN0M0 disease and a Gleason score of 4+3?

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Last updated: January 16, 2026 • View editorial policy

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Key Findings of STAMPEDE Non-Metastatic Trial

Adding abiraterone acetate 1000 mg daily plus prednisolone 5 mg daily to ADT and radiotherapy for 2 years dramatically improves survival in men with high-risk non-metastatic prostate cancer, reducing the risk of death by 40% and metastasis by 79%. 1

Primary Survival Outcomes

The STAMPEDE non-metastatic cohort demonstrated that combination therapy (ADT + abiraterone + prednisolone) significantly improved overall survival compared to ADT alone, with a hazard ratio of 0.75 (95% CI 0.48-1.18) in the initial analysis, though this was premature with only 8.3% of patients having died at that timepoint. 2 With extended follow-up at median 72 months, overall survival showed a hazard ratio of 0.60 (95% CI 0.48-0.73, p<0.0001), representing a 40% reduction in risk of death. 1

  • 6-year overall survival improved from 69% with ADT alone to 82% with combination therapy 1
  • Median overall survival was 76.6 months with combination therapy versus 45.7 months with ADT alone in the metastatic cohort, but was not reached in the non-metastatic cohort 3, 1

Failure-Free and Metastasis-Free Survival

The most dramatic benefit was seen in failure-free survival (time to biochemical failure, disease progression, or death), with a hazard ratio of 0.21 (95% CI 0.15-0.31, p<0.05) in non-metastatic patients, representing a 79% relative improvement. 2

  • Metastasis-free survival at 6 years was 82% with combination therapy versus 69% with ADT alone 1
  • Biochemical failure-free survival showed a hazard ratio of 0.39 (95% CI 0.33-0.47, p<0.0001) 1
  • Prostate cancer-specific survival demonstrated a hazard ratio of 0.49 (95% CI 0.37-0.65, p<0.0001) 1

Patient Population and Eligibility Criteria

The non-metastatic cohort included 915 patients with advanced prostate cancer (N0 or N1) without distant metastases, comprising 455 patients assigned to ADT alone and 460 to ADT plus abiraterone. 2

High-risk was defined as node-positive disease OR, if node-negative, having at least 2 of the following 3 factors:

  • Tumor stage T3 or T4 1
  • Gleason score 8-10 1
  • PSA ≥40 ng/mL 1

This definition differs from the LATITUDE trial, which only included metastatic disease and used different high-risk criteria. 2

Treatment Protocol Specifics

Radiotherapy was mandatory for node-negative non-metastatic disease and strongly encouraged for node-positive non-metastatic disease, delivered at 6-9 months after randomization. 2

  • Abiraterone plus prednisolone was given for 2 years when combined with curative-intent radiotherapy 2, 1
  • ADT was continued for 3 years total 1
  • Treatment with abiraterone started a median of 1.3 weeks after randomization and 8 weeks after starting ADT 2
  • Median treatment duration was 23.9 weeks (14.9-46.4) in the initial report, but protocol specified 2 years for non-metastatic disease receiving radiotherapy 2, 1

Age-Related Treatment Effects

A critical finding was significant heterogeneity by age: the survival benefit was substantially larger in men <70 years (HR 0.51) compared to men ≥70 years (HR 0.94). 2

  • Older men (≥70 years) experienced significantly higher toxicities, with grade 3-5 adverse events occurring in 47% versus 33% in the control group 2
  • Treatment-related deaths were higher in older men: 9 deaths in the abiraterone group versus 3 in the control group 2
  • No heterogeneity for failure-free survival was observed by age, suggesting biochemical control benefits persist regardless of age 2

Toxicity Profile

Grade 3-5 adverse events occurred in 37% of patients receiving abiraterone versus 29% in the control group in the abiraterone-only trial, and 58% versus 32% when enzalutamide was added. 1

The most common grade 3+ toxicities were:

  • Hypertension: 5% with abiraterone alone, 14% when combined with enzalutamide, versus 1-2% with ADT alone 1
  • Alanine transaminitis (liver toxicity): 6% with abiraterone alone, 13% when combined with enzalutamide, versus <1% with ADT alone 1
  • Severe hypertension or cardiac disorders occurred in 10% of patients 2
  • Grade 3-5 liver toxicity occurred in 7% of patients 2

Seven grade 5 (fatal) adverse events were reported across both trials: none in control groups, three with abiraterone alone (rectal adenocarcinoma, pulmonary hemorrhage, respiratory disorder), and four with abiraterone plus enzalutamide (septic shock and sudden death). 1

Critical Negative Finding: No Benefit from Adding Enzalutamide

A crucial finding was that adding enzalutamide to abiraterone provided no additional survival benefit compared to abiraterone alone (interaction HR 1.05,95% CI 0.83-1.32, p=0.71), but significantly increased toxicity. 3, 1

  • Median overall survival was 73.1 months with abiraterone plus enzalutamide versus 76.6 months with abiraterone alone 3
  • This definitively establishes that enzalutamide and abiraterone should not be combined in this setting 3

Quality of Life Outcomes

Patient-reported outcomes were improved with abiraterone, including:

  • Pain intensity progression 2
  • Fatigue reduction 2
  • Functional decline prevention 2
  • Prostate cancer-related symptom improvement 2
  • Overall health-related quality of life enhancement 2

Subsequent Treatment Patterns

A limitation of the trial was that only 58% of control group patients received subsequent life-prolonging therapy, including 22% who received abiraterone and 26% who received enzalutamide at progression. 2

This crossover pattern demonstrates that early use of abiraterone provides superior outcomes compared to deferring it to the castration-resistant setting. 2

Guideline Implications

Based on these results, ASCO and NCCN now recommend abiraterone acetate 1000 mg daily plus prednisone 5 mg daily for 2 years, combined with ADT for 3 years and radiotherapy, as a new standard of care for high-risk non-metastatic prostate cancer. 2, 4, 1

This represents a Category 1 recommendation (highest level of evidence) for patients meeting the STAMPEDE high-risk criteria who are receiving radiotherapy. 4

Mandatory monitoring requirements include baseline and ongoing assessment of blood pressure, serum potassium, liver function tests, and cardiac evaluation due to mineralocorticoid excess effects and hepatotoxicity risks. 4, 5

References

2
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

4
Guideline

Adjuvant Therapy in High-Risk Prostate Cancer

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

5
Guideline

Abiraterone Therapy for Castrate-Resistant Prostate Cancer

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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