Evolving Management Options for High-Risk Prostate Cancer

Up to 50% of men with prostate cancer who undergo curative intent local therapy (surgery/radiotherapy) experience biochemical failure (rising prostate-specific antigen [PSA]). Short PSA doubling times (<9 months) have been shown to correlate with more-rapid disease progression and death from prostate cancer.

Investigators conducted a pharmaceutical-sponsored, multinational, phase 3 study to evaluate the safety and efficacy of enzalutamide plus the luteinizing-hormone-releasing hormone agonist leuprolide compared with leuprolide alone in patients with prostate cancer and high-risk biochemical failure.

Eligible patients had PSA doubling times of ≤9 months after definitive local treatment, serum testosterone levels ≥150 ng/dL, and no evidence of metastatic disease on computed tomography and bone-scan imaging. A total of 1068 patients were randomized to receive enzalutamide plus leuprolide, placebo plus leuprolide, or enzalutamide monotherapy. Patients' median age was 69 years, 83% were white, the median PSA doubling time was 4.9 months, and the median PSA was 5.2 ng/mL.

At a median follow-up of 60.7 months, metastasis-free survival (MFS) was 87.3% in the combination arm, 71.4% in the leuprolide arm, and 80.0% in the enzalutamide arm. MFS was superior in the combination arm compared to the leuprolide arm (hazard ratio, 0.42; P<0.001) — the primary end point. MFS was also improved in the enzalutamide monotherapy arm compared with the leuprolide arm (HR, 0.63; P=0.005). While no new safety signals emerged, there was more treatment-related toxicity in the combination arm than in the leuprolide arm.