Apalutamide (androgen receptor inhibitor) + perioperative ADT improves 5-year MFS in high-risk localized/locally advanced prostate cancer undergoing prostatectomy

Apalutamide is an oral androgen receptor pathway inhibitor added to standard androgen-deprivation therapy (ADT) to intensify perioperative systemic control around radical prostatectomy. In the Phase 3 double-blind PROTEUS trial (NCT03767244), men with newly diagnosed high-risk localized or locally advanced prostate cancer were randomized to ADT+apalutamide 240mg daily vs ADT+placebo for 6×28-day cycles pre-op and post-op (n=2109; median follow-up 61.7 months). Dual primaries both hit: pCR/minimal residual disease was 8.9% vs 1.0% (OR 10.17; p<0.001) and 5-year metastasis-free survival was 78.2% vs 73.5% (HR for distant metastasis or death 0.80; p=0.02); event-free survival, time to first subsequent treatment, and time to distant metastasis also favored apalutamide (all p<0.001). Grade 3/4 AEs were higher with apalutamide (39.6% vs 31.0%), driven mainly by rash—so the efficacy delta comes with a real tolerability tax versus perioperative ADT alone.