Cytoreduction and androgen signaling modulation by abiraterone acetate (AA) plus leuprolide acetate (LHRHa) versus LHRHa in localized high-risk prostate cancer (PCa): Preliminary results of a randomized preoperative study.

4556 Background: Endocrine to “intracrine” androgen signaling transition, a milestone in the lethal progression of PCa, has not been characterized in localized high risk disease. Signaling heterogeneity under the selective pressure of castration may account for response differences. Methods: A single institution preoperative study of 12 weeks AA 1g/prednisone 5 mg + LHRHa compared to LHRHa (randomized 2:1) was conducted in patients (pts) with high risk PCa (clinical stage ≥T1c and biopsy Gleason score ≥8, or ≥T2b, Gleason ≥ 7 and PSA > 10ng/ml). Primary aim: Assess difference in down staging (≤ ypT2) and safety. Secondary aims: Assess difference in androgen biosynthesis, androgen signaling (AR, AR variants, NKX 3.1, ERG, PSA) proliferation apoptosis and candidate treatment resistance pathways. Results: We report on 37 (50 enrolled) pts who had prostatectomy. AA+LHRHa was given to 25pts, LHRHa to 12. Median age is 61 ys (46-74). Preoperative PSA was <0.1ng/ml in 17/25 (68%) AA+LHRHa vs 0/12 LHRHa (p 0.0001...