PURPOSE: Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone-releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression.
PATIENTS AND METHODS: A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy.
RESULTS: The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ4-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node-positive disease in the majority.
CONCLUSION: LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden.
Written by:
Taplin ME, Montgomery B, Logothetis CJ, Bubley GJ, Richie JP, Dalkin BL, Sanda MG, Davis JW, Loda M, True LD, Troncoso P, Ye H, Lis RT, Marck BT, Matsumoto AM, Balk SP, Mostaghel EA, Penning TM, Nelson PS, Xie W, Jiang Z, Haqq CM, Tamae D, Tran N, Peng W, Kheoh T, Molina A, Kantoff PW. Are you the author?
Institution(s): See publishing journal.
Reference: J Clin Oncol. 2014 Nov 20;32(33):3705-15.
doi: 10.1200/JCO.2013.53.4578
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PubMed Abstract
PMID: 25311217