- Design
- Post hoc analysis of a randomised platform trial with linked health records
- Population
- 6,292 men starting long-term ADT for high-risk localised or metastatic prostate cancer
- Primary outcome
- Major adverse cardiovascular events; SCORE2 performance
- Effect
- 5-year MACE 7-9%; abiraterone M1 SDHR 1.36 (0.87-2.10); SCORE2 AUC 0.61-0.63
This post hoc analysis of the STAMPEDE platform trial linked 6,292 English participants to health records. Men had started long-term androgen deprivation therapy for high-risk localised or metastatic prostate cancer, with or without intensification by abiraterone and prednisolone, abiraterone plus enzalutamide, docetaxel, zoledronic acid or prostate radiotherapy.
Five-year major adverse cardiovascular event rates with androgen receptor pathway inhibitor intensification were 9% in non-metastatic and 7% in metastatic disease, comparable with ADT alone. No intensification was associated with a statistically significant increase: for abiraterone, subdistribution hazard ratios were 1.15 (0.80 to 1.67) in non-metastatic and 1.36 (0.87 to 2.10) in metastatic disease. Previous cardiovascular disease was the strongest predictor. SCORE2 discriminated poorly (AUC 0.61 to 0.63) and underestimated absolute risk.
The practical message is twofold. Cardiovascular fears should not by themselves stop intensification that improves survival. But the intervals allow a meaningful increase, men with severe heart disease were under-represented, and standard risk tools underestimate risk here, so cardiovascular assessment and risk-factor treatment should be part of starting hormone therapy.
- Do not withhold survival-improving intensification on cardiovascular grounds alone.
- Assess blood pressure, lipids, glucose and smoking when starting long-term ADT.
- Expect SCORE2 to underestimate risk in men starting hormone therapy for prostate cancer.
- Involve primary care or cardiology for men with established cardiovascular disease.
Why it matters
Cardiovascular disease is a leading non-cancer cause of death in these men, and the usual calculator misjudges it.
Don't overread it
A post hoc analysis with wide intervals; a moderate increase in events was not excluded.
The statistics, in plain English
An interval of 0.87 to 2.10 means the data fit anything from a small reduction to a doubling of events, so 'no significant increase' is not the same as 'no increase'. An AUC around 0.62 means SCORE2 ranked risk correctly only a little better than chance.
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