EVIDENCE from a recent clinical trial has provided important clarity for patients and clinicians managing high-risk biochemically recurrent prostate cancer. The study compared three treatment approaches: enzalutamide plus leuprolide, leuprolide alone, and enzalutamide monotherapy. While earlier findings already demonstrated improvements in metastasis-free survival, this final analysis focused on overall survival outcomes, which are crucial for long-term treatment decisions.
Patients in the trial were randomly assigned in a 1:1:1 ratio to the three treatment groups and followed over several years. The primary endpoint originally focused on metastasis-free survival, with overall survival as a key secondary measure.
Benefits of Enzalutamide Plus Leuprolide
The results showed that enzalutamide plus leuprolide offered a clear survival advantage. After eight years, overall survival reached 78.9% in the combination group, compared with 69.5% among those receiving leuprolide alone. This equated to a 40% reduction in the risk of death (hazard ratio 0.60), a statistically significant improvement.
In contrast, enzalutamide monotherapy did not outperform leuprolide alone, with an 8-year survival rate of 73.1%. Although this suggests that monotherapy remains clinically acceptable for some patients, it does not provide the same survival benefit as the combined approach.
Secondary endpoints, such as time to additional antineoplastic therapy and time to first skeletal symptoms, aligned with previously reported outcomes and continued to favour the combination treatment. Safety profiles also remained consistent, with no unexpected concerns.
These findings are particularly relevant for men experiencing biochemically recurrent prostate cancer, where PSA levels rise despite earlier treatment. Selecting therapies that offer both metastasis-free and overall survival benefits is essential for improving long-term outcomes and preserving quality of life.
In clinical practice, enzalutamide plus leuprolide may now be considered a strong option for patients with high-risk biochemical recurrence who are suitable for combination hormone therapy. While treatment decisions should remain personalised, the evidence strongly supports this approach as an effective strategy in delaying disease progression and improving survival prospects.
Reference
Shore ND et al. Improved survival with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2025;DOI:10.1056/NEJMoa2510310.
