Final oncological outcomes of the randomized phase II trial ARNEO: Neoadjuvant degarelix with or without apalutamide prior to radical prostatectomy for high-risk prostate cancer.
Authors: Alexander Giesen, Gaëtan Devos, Lorenzo Tosco, Marcella Baldewijns, Thomas Gevaert, Karolien Goffin, Niloefar Ahmadi Bidakhvidi, Annouschka Laenen, Yannic Raskin, Carl Van Haute, Lieven Goeman, Gert de Meerleer, Charlien Berghen, Wout Devlies, Frank Claessens, Hendrik Van Poppel, Wouter Everaerts, Steven Joniau
Journal: Journal of Clinical Oncology (2025)

394 Background: High-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence (BCR) and metastatic progression following local therapy. The ARNEO trial is a double-blind, placebo-controlled trial, evaluating the role of neoadjuvant degarelix with or without apalutamide before radical prostatectomy (RP) in men with high-risk PCa. Previously, we demonstrated that patients receiving neoadjuvant degarelix + apalutamide (n=45) had significantly better pathological response in terms of pT2 disease (51% vs. 27%; p=0.022) and minimal residual disease (MRD) (37.8% vs. 9.1%, p=0.002) compared to patients receiving degarelix alone (n=44). However, it was yet unclear if these improved pathological outcomes were also associated with improved oncological outcomes. Methods: High-risk PCa patients were randomly assigned 1:1 to degarelix + apalutamide versus degarelix + placebo for 12 weeks followed by radical prostatectomy. Follow-up of patients included PSA and testosterone testing every 6 months. No adjuvant radiotherapy was given. However, at time of PSA relapse (PSA &gt;0.2 ng/ml) patients received a PSMA PET/CT. In case of negative imaging at time of BCR, patients received salvage radiotherapy to the prostate bed (+/- pelvic region). Results: All patients had a minimum follow-up of 36 months. Median follow-up was 46.5 months (IQR 42-53.5) in the degarelix + placebo arm and 46 months (IQR 42-53) in the degarelix + apalutamide arm. Median time to testosterone recovery (&gt;50 ng/dl) was 6 and 7 months, respectively ( p = 0.15 ). In total, 14 (31%) patients in the degarelix + apalutamide arm developed BCR compared to 18 (41%) patients in the placebo arm (p=0.3). No statistically significant difference in BCR was observed between patients who achieved MRD and patients without MRD at final pathology (35% vs 38%; p = 1 ). However, ypT2 disease at final pathology was highly associated with improved BCR-free survival (11% vs 52%; p &lt; 0.0001 ). Finally, we also looked at the prognostic value of achieving specimen-confined disease (SCD; defined as ypT2-3a AND negative surgical margins AND pN0). Patients with SCD at final pathology also had a significantly better BCR-free survival, compared to those patients without SCD (18% vs 65%; p &lt; 0.0001 ). Conclusions: At 3 years follow-up, no statistically significant difference in terms of BCR was observed between patients treated with neoadjuvant degarelix + apalutamide or degarelix alone. MRD was not associated with improved BCR-free survival. However, ypT2 and SCD disease following neoadjuvant hormonal therapy was highly associated with improved BCR-free survival, suggesting that ypT2 and SCD disease might be used as a surrogate endpoints for improved BCR-free survival. Clinical trial information: NCT03080116 .