Apalutamide + Abiraterone acetate plus Prednisone (AAP) + Leuprolide with Stereotactic, Ultra-Hypofractionated Radiation (AASUR) in Very High Risk Prostate Cancer: A Single Arm, Phase 2 Study.

Abstract

This study investigates a short-course, intensified regimen combining apalutamide, abiraterone acetate and prednisone (AAP), and stereotactic body radiotherapy to reduce treatment burden and improve disease control in a very high-risk population (VHR) inadequately represented in prior trials. This multi-institutional, single-arm phase 2 trial enrolled patients with VHR localized prostate cancer, defined per NCCN as histologically confirmed adenocarcinoma with ≥2 high-risk features: Gleason 8-10, PSA ≥20, clinical/radiographic ≥T3, or >4 cores of Gleason 8 disease. Patients received 6 months of apalutamide, abiraterone acetate and leuprolide plus prostate/seminal vesicle-directed ultra-fractionated SBRT. The primary endpoint was 3-year biochemical recurrence (BCR) rate by Phoenix criteria, with a prespecified superiority threshold of <10%. Secondary endpoints included PSA ≥ 0.2, metastasis-free survival (MFS), and time to testosterone recovery >150 ng/dL. Between 08/2016 to 12/2022, 63 patients were treated. At 3 years, the Phoenix-defined BCR rate was 19.0%. Biochemical recurrence-free survival (bRFS) was 84.2% (95 CI, 75.6-93.7) with median follow-up of 41 months (34-43). Three-year MFS was 93.6% (95% CI, 87.8%-99.8%), with no deaths observed. Median time to testosterone recovery >150 ng/dL was 6 months (range, 3-24). No new safety signals emerged, and the only significant quality-of-life decline was in the EPIC sexual sub-domain at 12 months. Treatment intensification with apalutamide, AAP, ADT and SBRT well-tolerated with limited impact on quality of life. While BCR rates exceed the superiority threshold, outcomes aligned with historical benchmarks, supporting further evaluation of the regimen in prospective trials.