Apalutamide (AR antagonist) + ADT periop boosts pCR/MRD and improves 5-year MFS after prostatectomy in high-risk localized/locally advanced disease

Apalutamide (APA), an androgen receptor inhibitor, was added to androgen deprivation therapy (ADT) perioperatively (6 months neoadjuvant, then 6 months adjuvant) around radical prostatectomy (RP) in the double-blind Phase 3 PROTEUS trial (NCT03767244) in newly diagnosed high-risk localized or locally advanced prostate cancer (n=2109; GS≥8 in 95.8%; cN0/cN1 allowed on conventional imaging; median follow-up 61.7 months). APA+ADT improved both co-primary endpoints vs placebo+ADT: pCR/MRD (≤ypT2 and ≤5 mm) 8.9% vs 1.0% (OR 10.17; p<0.0001) and BICR MFS HR 0.80 (p=0.0169) with 5-year MFS 78.2% vs 73.5% (median NR); key secondaries also favored APA+ADT (EFS HR 0.71; median 57.1 vs 38.4 months; TTST1 HR 0.65; TTDM HR 0.68). Safety moved as expected for intensified AR-pathway blockade: grade 3/4 TEAEs 39.6% vs 31.0% and discontinuations due to TEAEs 7.4% vs 2.7%; importantly, this is a meaningful advance over surgery±(neo)adjuvant conventional ADT strategies that historically improved pathologic features without clear survival benefit.