期刊
EUROPEAN UROLOGY
卷 76, 期 4, 页码 418-424出版社
ELSEVIER
DOI: 10.1016/j.eururo.2019.05.010
关键词
High-risk localised prostate cancer; Glucocorticoid receptor; Abiraterone acetate; Androgen deprivation therapy; Neoadjuvant; Preoperative; Radical prostatectomy; Androgen receptor splice variant; Androgen receptor Tumour volume
资金
- Prostate Cancer Foundation
- Janssen Research Development
Optimal therapeutic strategy remains an unmet need in localised high-risk prostate cancer (LHRPC). Androgen biosynthesis inhibition in the preoperative setting may improve outcomes. In this single-centre randomised trial, we looked at therapy outcomes of preoperative treatment with abiraterone acetate + prednisone (AAP) + luteinising hormone-releasing hormone agonist (LHRHa) or LHRHa alone followed by radical prostatectomy in 65 men. We did not see a significant difference of organ-confined carcinoma (p = 0.27). However, tumour volume measures were significantly lower for AAP + LHRHa treatment (p <= 0.001). Of note, lower tumour epithelium volume correlated with improved biochemical recurrence-free survival at >= 4-yr follow-up (p = 0.0014). Tumours pretreated with AAP + LHRHa had lower proliferation and androgen signalling expression than LHRHa. On multivariate analysis, glucocorticoid receptor (GR) overexpression correlated with persistent tumours in AAP + LHRHa (p = 0.018). The presence of nuclear androgen receptor splice variant (nARV7) correlated with persistent tumours in both arms. No new safety signals were observed. This is the first study investigating the role of preoperative AAP + LHRHa versus LHRHa alone in LHRPC. We report significant cytoreduction by tumour volume measures inversely correlating with biochemical relapse. Validation of these proposed tumour volume measures is planned. A potential role of GR in resistance to androgen biosynthesis inhibition warrants further study. Patient summary: This is the first study of abiraterone acetate plus leuprolide versus leuprolide alone in high-risk localised prostate cancer followed by prostatectomy. Patients in the combination arm had a significantly smaller tumour size. (C) 2019 Published by Elsevier B.V. on behalf of European Association of Urology.
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