Alessandro Rizzo1, Veronica Mollica2, Matteo Rosellini2, Andrea Marchetti2, Angela Dalia Ricci2, Michelangelo Fiorentino3, Nicola Battelli4, Matteo Santoni4, Francesco Massari2. 1. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy. Electronic address: rizzo.alessandro179@gmail.com. 2. Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni - 15, Bologna, Italy. 3. Department of Specialistic Diagnostic and Experimental Medicine, University of Bologna, Via Massarenti 9, Bologna, 40138, Italy. 4. Oncology Unit, Macerata Hospital, via Santa Lucia 2, Macerata, 62100, Italy.
Abstract
BACKGROUND: The Androgen Receptor Splice Variant 7 (AR-V7) has been associated with poor clinical outcomes in patients with castration-resistant prostate cancer (CRPC). Herein, we performed a meta-analysis aimed at systematically exploring the association between metastatic sites and AR-V7 expression in CRPC patients across prospective clinical trials. METHODS: We retrieved all the relevant prospective clinical trials through PubMed/Medline, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included metastatic sites (lymph node metastases, any site metastases, visceral metastases, and bone metastases) in AR-V7 positive and AR-V7 negative CRPC patients. Odds Ratios (ORs) and 95 % confidence intervals (CI) were calculated. RESULTS: Overall, 14 eligible prospective studies involving a total of 1944 CRPC patients (AR-V7 positive: 467; AR-V7 negative: 1477) were included in the analysis. According to our results, no differences between AR-V7 positive and AR-V7 negative CRPC patients were observed in terms of lymph node (OR 1.01; 95 % CI 0.49-2.09) and visceral metastases (OR 1.23; 95 % CI 0.89-1.71). Conversely, AR-V7 positive CRPC patients presented higher rate of any site metastases (OR 2.22; 95 % CI 1.58-3.12) and bone metastases (OR 2.03; 95 % CI 1.42-2.9) compared to AR-V7 negative subjects. CONCLUSIONS: The results of this meta-analysis, the first in literature to be specifically focused on this topic so far, suggest that AR-V7 positivity may be associated with any site metastases and bone metastases; conversely, no association has been highlighted between AR-V7 expression and lymph node or visceral metastases. Although this meta-analysis should be interpreted with caution due to some limitations, our findings confirm that AR-V7 status could designate a unique and peculiar subtype of PC. Further studies aimed at improving and standardizing AR-V7 detection in clinical trials on CRPC patients are warranted.
BACKGROUND: The Androgen Receptor Splice Variant 7 (AR-V7) has been associated with poor clinical outcomes in patients with castration-resistant prostate cancer (CRPC). Herein, we performed a meta-analysis aimed at systematically exploring the association between metastatic sites and AR-V7 expression in CRPC patients across prospective clinical trials. METHODS: We retrieved all the relevant prospective clinical trials through PubMed/Medline, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included metastatic sites (lymph node metastases, any site metastases, visceral metastases, and bone metastases) in AR-V7 positive and AR-V7 negative CRPC patients. Odds Ratios (ORs) and 95 % confidence intervals (CI) were calculated. RESULTS: Overall, 14 eligible prospective studies involving a total of 1944 CRPC patients (AR-V7 positive: 467; AR-V7 negative: 1477) were included in the analysis. According to our results, no differences between AR-V7 positive and AR-V7 negative CRPC patients were observed in terms of lymph node (OR 1.01; 95 % CI 0.49-2.09) and visceral metastases (OR 1.23; 95 % CI 0.89-1.71). Conversely, AR-V7 positive CRPC patients presented higher rate of any site metastases (OR 2.22; 95 % CI 1.58-3.12) and bone metastases (OR 2.03; 95 % CI 1.42-2.9) compared to AR-V7 negative subjects. CONCLUSIONS: The results of this meta-analysis, the first in literature to be specifically focused on this topic so far, suggest that AR-V7 positivity may be associated with any site metastases and bone metastases; conversely, no association has been highlighted between AR-V7 expression and lymph node or visceral metastases. Although this meta-analysis should be interpreted with caution due to some limitations, our findings confirm that AR-V7 status could designate a unique and peculiar subtype of PC. Further studies aimed at improving and standardizing AR-V7 detection in clinical trials on CRPC patients are warranted.
Authors: Seaho Kim; CheukMan C Au; Mohd Azrin Bin Jamalruddin; Naira Essam Abou-Ghali; Eiman Mukhtar; Luigi Portella; Adeline Berger; Daniel Worroll; Prerna Vatsa; David S Rickman; David M Nanus; Paraskevi Giannakakou Journal: Elife Date: 2022-07-18 Impact factor: 8.713