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

PURPOSE: This study investigates a short-course, intensified regimen combining apalutamide, abiraterone acetate, and prednisone (AAP) and stereotactic body radiotherapy (SBRT) to reduce treatment burden and improve disease control in a very high-risk (VHR) population inadequately represented in prior trials.

PATIENTS AND

METHODS

This multi-institutional, single-arm, phase 2 trial enrolled patients with VHR localized prostate cancer, defined according to the National Comprehensive Cancer Network as histologically confirmed adenocarcinoma with ≥2 high-risk features: Gleason score 8 to 10, prostate-specific antigen (PSA) ≥20, clinical or radiographic ≥T3, or >4 cores containing Gleason score 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 ng/mL, metastasis-free survival (MFS), and time to testosterone recovery >150 ng/dL.

RESULTS

Between August 2016 and December 2022, 63 patients were treated. At 3 years, the Phoenix-defined BCR rate was 19%. BCR-free survival was 84.2% [95% confidence interval (CI), 75.6-93.7] with a median follow-up of 41 months (34-43). The 3-year MFS was 93.6% (95% CI, 87.8%-99.8%), with no deaths observed. The median time to testosterone recovery >150 ng/dL was 6 months (range, 3-24 months). No new safety signals emerged, and the only significant quality-of-life (QOL) decline was in the EPIC sexual subdomain at 12 months.

CONCLUSIONS

Treatment intensification with apalutamide, AAP, androgen deprivation therapy, and SBRT was well-tolerated with limited impact on QOL. Although BCR rates exceed the superiority threshold, outcomes aligned with historic benchmarks, supporting further evaluation of the regimen in prospective trials.