Results of the Randomized Phase 3 AFU-GETUG-20 Trial Evaluating Adjuvant Leuprorelin Acetate After Radical Prostatectomy in Men with High-risk Localized Prostate Cancer

Abstract

Background and objective: Androgen-deprivation therapy survival benefits after radical prostatectomy (RP) in nonmetastatic high-risk prostate cancer (PCa) patients with an undetectable prostate-specific antigen (PSA) level are unclear. The AFU-GETUG-20 study assessed the benefit of leuprorelin immediately after RP in this population.

Methods: This open-label, randomized, phase 3 trial is conducted at 37 French centers. Participants undergoing RP for nonmetastatic PCa were aged ≥18 yr, with a postoperative Gleason score of ≥7 and PSA <0.1 ng/ml. Participants were randomly assigned (1:1) to the observation or leuprorelin (45 mg subcutaneous Q6M, 24 mo) arm. The primary endpoint was metastasis-free survival in the intent-to-treat population (n = 322). The secondary objectives PSA and testosterone level evolution, PCa-specific survival, overall survival, safety, and quality of life.

Key findings and limitations: From 2011 to 2017, 325 patients were randomized to the observation (n = 163) or leuprorelin (n = 162) arm. The 10-yr risk of metastasis occurrence was similar between arms (hazard ratio [HR] 0.63 [95% confidence interval {CI} 0.30-1.30]; p = 0.204) with no differences in PSA rise-free survival (HR 0.74 [95% CI 0.47-1.16]; p = 0.187), overall survival (HR 1.24 [95% CI 0.56-2.76]; p = 0.596), or PCa-specific survival (HR 0.57 [95% CI 0.10-3.17]; p = 0.512). Leuprorelin-treated patients had lower testosterone level after surgery (p < 0.001), shorter time to global health degradation (p = 0.0019), fatigue (p < 0.001), pain (p < 0.001), and additional adverse events, mainly hot flashes (83.6% vs 6.2%), pain (57.2% vs. 17.1%), fatigue (45.4% vs 16.3%), and psychiatric disorders (25.0% vs 2.3%). Insufficient enrollment affected the trial power but permitted pertinent comparison.

Conclusions and clinical implications: Leuprorelin treatment immediately after RP in high-risk nonmetastatic PCa patients with an undetectable PSA level does not improve survival, but increases adverse events, leading to poorer quality of life compared with observation.

Keywords: AFU-GETUG-20; Gonadotropin-releasing hormone receptor agonist; High-risk prostate cancer; Immediate androgen-deprivation therapy; Leuprorelin acetate; Radical prostatectomy; Undetectable prostate-specific antigen level.