Recent findings from a post hoc analysis of the Phase 3 EMBARK trial, presented at the 2025 Southeastern Section of the American Urological Association (SESAUA) annual meeting, demonstrate the significant potential of enzalutamide in controlling prostate-specific antigen (PSA) levels among patients with high-risk biochemically recurrent prostate cancer.

The study examined patients with a PSA doubling time of nine months or less, indicative of aggressive disease progression following definitive treatment. Participants were randomly assigned to three distinct treatment strategies: enzalutamide combined with leuprolide, leuprolide alone, or enzalutamide alone. Researchers closely monitored PSA dynamics to evaluate the effectiveness of these treatments.

Notably, by week 25, a substantial majority of patients receiving enzalutamide combined with leuprolide (89%) or as monotherapy (82%) achieved undetectable PSA levels, significantly outperforming those receiving leuprolide alone (63%). Additionally, treatment suspension at week 37 due to successful PSA suppression occurred more frequently among patients treated with enzalutamide, highlighting its efficacy.

Following treatment suspension, upon a subsequent rise in PSA necessitating treatment reinitiation, enzalutamide continued to demonstrate superior performance. Impressively, 96% of patients on combined therapy and 90% on monotherapy returned to undetectable PSA levels, compared to only 73% of those treated solely with leuprolide.

Crucially, achieving undetectable PSA after treatment reinitiation correlated with improved metastasis-free survival across all groups independently from the treatment, reinforcing the clinical significance of robust PSA control.

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