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.

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 >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 (>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 < 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 < 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 .