Background: Treatment options for high-risk localized prostate cancer remain inadequate, with most pts relapsing despite local therapy. We conducted a phase II multicenter trial of neoadjuvant D +B prior to radical prostatectomy in pts with high-risk localized prostate cancer. Methods: Eligibility included any of the following: PSA >20 ng/mL or PSA velocity >2 ng/mL/yr, cT3 disease, any biopsy Gleason 8-10, Gleason 7 with T3 disease by endorectal (er) MRI. In addition, pts with ≥50% biopsy cores involved and either Gleason 7 or PSA >10 or cT2 disease were eligible. Pts were treated with D 70 mg/m² q3 weeks x 6 cycles and B 15 mg/m² q3 weeks x 5 cycles. The primary end point was erMRI partial response (PR, defined as ≥50% decrease in tumor volume) in a single target lesion after chemotherapy. Results: 42 pts were enrolled, and 41 were treated. Median age was 55 yrs (range, 40-66 yrs). Baseline characteristics included: median PSA 10.1 ng/mL (range, 2.1-72.4 ng/mL), cT2 49%, cT3 32%, and Gleason 8-10 73%. Thirty-eight of 41 (93%) pts completed all 6 cycles. Grade ≥ 3 adverse events included hyperglycemia (1/41), allergic reaction (1/41), cough, lymphopenia (3/41), and febrile neutropenia (3/41). Thirty-seven of the 41 pts underwent radical prostatectomy. Reasons for not proceeding with surgery included: a bladder neck injury, positive lymph nodes, and withdrawal of consent in 2 pts. Response data are shown in the Table. No pts achieved a complete pathologic response. Conclusions: Neoadjuvant D+B demonstrates clinical activity in men with high-risk localized prostate cancer. The role of neoadjuvant chemotherapy in prostate cancer, and perioperative antiangiogenic therapy in solid tumors in general, requires further elucidation through ongoing and planned randomized trials.