Τίτλος:
Clinical and Biological Characterisation of Localised High-risk Prostate Cancer: Results of a Randomised Preoperative Study of a Luteinising Hormone-releasing Hormone Agonist with or Without Abiraterone Acetate plus Prednisone
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Neoadjuvant therapy with abiraterone acetate + prednisone (AAP) + luteinising hormone-releasing hormone agonist (LHRHa) induced significant cytoreduction associated with a lack of recurrence versus LHRHa, though staging did not differ significantly. This first randomised AAP study in localised high-risk prostate cancer explores response heterogeneity and associated molecular effects to guide further research. © 2019
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. © 2019
Συγγραφείς:
Efstathiou, E.
Davis, J.W.
Pisters, L.
Li, W.
Wen, S.
McMullin, R.P.
Gormley, M.
Ricci, D.
Titus, M.
Hoang, A.
Zurita, A.J.
Tran, N.
Peng, W.
Kheoh, T.
Molina, A.
Troncoso, P.
Logothetis, C.J.
Περιοδικό:
European urology oncology
Λέξεις-κλειδιά:
abiraterone acetate; glucocorticoid receptor; gonadorelin agonist; prednisone; abiraterone acetate; antineoplastic agent; gonadorelin; prednisone, anemia; Article; cell proliferation; controlled study; fatigue; high risk population; hot flush; human; hyperbilirubinemia; hypercholesterolemia; hyperglycemia; hypertension; hypertransaminasemia; immunohistochemistry; insomnia; major clinical study; male; neoadjuvant therapy; preoperative evaluation; priority journal; prostate cancer; prostatectomy; randomized controlled trial; recurrence free survival; treatment outcome; tumor volume; aged; clinical trial; drug combination; middle aged; pathology; phase 2 clinical trial; preoperative period; prostate tumor; risk assessment, Abiraterone Acetate; Aged; Antineoplastic Agents; Drug Combinations; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prednisone; Preoperative Period; Prostatectomy; Prostatic Neoplasms; Risk Assessment
DOI:
10.1016/j.eururo.2019.05.010
