Journal
JOURNAL OF CLINICAL ONCOLOGY
Volume 37, Issue 11, Pages 923-+Publisher
AMER SOC CLINICAL ONCOLOGY
DOI: 10.1200/JCO.18.01777
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Funding
- Astellas Pharma
- Medivation
- Pfizer
- Fairweather Family Fund at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute
- Fat Boys/Slim Sisters Pan-Mass Challenge Fund at the Lank Center for Genitourinary Oncology at Dana-Farber Cancer Institute
- Prostate Cancer Foundation [16CHAS03, 142016]
- Prostate Cancer Clinical Trials Consortium
- Dana-Farber Cancer Institute Prostate Specialized Program of Research Excellence [P50CA090]
- Prostate Cancer Foundation Young Investigator Award
- Dana-Farber/Harvard Cancer Center Prostate Cancer Specialized Program of Research Excellence (National Cancer Institute) [P50CA090381]
- Department of Defense Impact Award [W81XWH-16-1-0433]
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PURPOSE 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. PATIENTS AND METHODS 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. RESULTS 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. CONCLUSION 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. (C) 2019 by American Society of Clinical Oncology
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