Background: Patients (pts) with localized high-risk PC have disease progression rates of ~50% after RP (Kane et al. J Urol. 2007). Neoadjuvant studies show that androgen blockade can improve local disease control at the time of RP (McKay et al. Prostate Cancer Prostatic Dis. 2017; Taplin et al. JCO. 2014; Efstathiou et al. Eur Urol. 2019). This study will determine if treatment with APA + ADT before RP in pts with localized high-risk or locally advanced PC improves pathologic complete response (pCR) rate and if neoadjuvant and adjuvant peri-operative treatment with APA + ADT improves metastasis-free survival (MFS) compared with PBO + ADT. Methods: This international multicenter trial is enrolling candidates for RP with localized high-risk or locally advanced PC. Eligibility criteria: any combination of Gleason score (GS) 4 + 3 (= Grade Group [GG] 3) and GS 8 (4 + 4 or 5 + 3) from ≥ 6 systematic biopsy cores (SB) or targeted biopsy cores (TB) (with ≥ 1 core GS 8 [4 + 4 or 5 + 3] included); any combination of GS 4 + 3 (= GG 3) and GS 8 (4 + 4 or 5 + 3) from ≥ 3 SB or TB (with ≥ 1 core GS 8 [4 + 4 or 5 + 3]) included and prostate-specific antigen (PSA) ≥ 20 ng/mL; GS ≥ 9 (GG 5) in ≥ 1 SB or TB; or ≥ 2 SB or TB with continuous GS ≥ 8 (GG 4), each with ≥ 80% involvement. Stratification: GS (7 or ≥ 8), cN0 or N1, and region. Randomization: 1:1 to APA (240 mg) + ADT or PBO + ADT. Pts will receive 6 months neoadjuvant treatment and RP + 6 months adjuvant treatment. Dual primary end points: pCR rate (assessed by blinded independent central pathology review) and MFS (assessed by blinded independent central radiology review). Secondary end points: PSA-free survival and progression-free survival. Imaging with CT or MRI and bone scan at screening, after RP, and then every 6 months following biochemical failure until documented distant metastasis, or death. ~1500 pts will be enrolled globally over 3 years at 240 sites in 19 countries. An independent data monitoring committee is commissioned to review trial data. Clinical trial information: NCT03767244