Abstract Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.
McBride et al. (Thu,) studied this question.