“Even with the current therapies, there is a huge unmet need for patients with high-risk prostate cancer,” said Prof. Steven Joniau (UZ Leuven, Belgium). A retrospective analysis suggested a survival benefit of neoadjuvant hormonal therapy prior to radical prostatectomy in patients with high-risk disease2. To confirm the results of this study prospectively, the phase 2 ARNEO trial (NCT03080116) was designed, which randomised 89 patients with high-risk prostate cancer to 3 months of neoadjuvant degarelix plus apalutamide therapy or to degarelix alone, prior to radical prostatectomy.
The primary endpoint, the proportion of patients with minimal residual disease (<0.25 mL) after neoadjuvant treatment, was met. In the experimental arm, 38% of the patients displayed minimal residual disease after treatment compared with 9% in the placebo arm (RR 4.2; P=0.002). Correspondingly, the median residual cancer burden was 1.7 mL in the placebo arm and 0.48 mL in the experimental arm. Furthermore, downstaging to pT2-disease occurred more often in the apalutamide arm than in the placebo arm (51% vs 27%; P=0.03). The authors found that PSMA levels and residual cancer volume were correlated, suggesting that PSMA has a monitoring role in future neoadjuvant trials. Finally, PTEN loss was associated with poor response to therapy (11% vs 43%; P=0.002).
Prof. Joniau concluded that the results of this phase 2 trial justify the development of phase 3 trials assessing neoadjuvant hormonal therapy in patients with high-risk prostate cancer.
1. Devos G, et al. Randomized phase II trial of neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for unfavorable intermediate- and high-risk prostate cancer. Game-changing session 3, EAU 2022, 01–04 July.
2. Tosco L, et al. Prostate Cancer Prostatic Dis. 2017;20:407-412