Evaluation of Intense Androgen Deprivation Before Prostatectomy: A Randomized Phase II Trial of Enzalutamide and Leuprolide With or Without Abiraterone.

Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer.

Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored.

Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP.

Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 Feb 27 [Epub ahead of print]

Rana R McKay, Huihui Ye, Wanling Xie, Rosina Lis, Carla Calagua, Zhenwei Zhang, Quoc-Dien Trinh, Steven L Chang, Lauren C Harshman, Ashley E Ross, Kenneth J Pienta, Daniel W Lin, William J Ellis, Bruce Montgomery, Peter Chang, Andrew A Wagner, Glenn J Bubley, Adam S Kibel, Mary-Ellen Taplin

1 University of California, San Diego, San Diego, CA., 3 Beth Israel Deaconess Medical Center, Boston, MA., 2 Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, MA., 4 Johns Hopkins Hospital, Baltimore, MD., 5 University of Washington, Seattle, WA.

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