Androgen-deprivation therapy (ADT) administered in neoadjuvant setting before radical prostatectomy (RP) represents an ideal in vivo human model to test the efficacy of hormonal treatments in prostate cancer (PCa). This review summarizes the findings from published studies specifically focused on the biological effects of ADT assessed on specimens from RP. The aim is to provide a base of knowledge that might be used to design future studies on neoadjuvant therapy for PCa.
A systematic review of the literature was performed according to the PRISMA statements. Search protocol identified published studies including a detailed analysis on specimen from RP to assess the biological effects of neoadjuvant ADT. In November 2017, Medline, Embase and Scopus databases were searched using the terms "neoadjuvant" AND ("hormone therapy" OR "androgen deprivation therapy") AND "prostate cancer" across the "Title/Abstract" fields. Effects of ADT were classified according to 4 pathways - suppression of cellular proliferation, induction of apoptosis, alteration of immune response and onset of hormonal refractiveness - and relative markers of response were identified.
From 1856 papers initially retrieved, 19 studies were finally selected and included into the present review. ADT was constituted by luteinizing hormone-releasing hormone (LH-RH) agonist alone in 2, peripheral anti-androgen alone in 1, both in 10, abiraterone acetato in 1, unspecified in 5. According to the 4 pathways above described, the following markers of response were identified: transcription of the oncogene TMPRSS2:ERG, translation of Aurora-A, coding of ß1C integrin gene, translation of ki-67, expression of nerve growth factors TrkA and p75NGFR, anti-angiogenic activity and micro-vessel density were involved into suppression of proliferation; mRNA transcription of bcl-2, expression of cleaved caspase-3 and translation of insulin growth factor binding protein 3, into induction of apoptosis; expression of IL-7 gene, programmed death-ligand 1, and increase of intra-prostatic T-cell population were related to alteration of immune response; finally, expression of heat shock protein 27 and de-differentiation of PCa to neuroendocrine cells, influenced the onset of hormonal refractiveness.
Despite a potential high interest, unexpectedly, only 19 heterogeneous studies investigated the effects of ADT through the analysis of specimens from RP. The present review summarizes the available evidences on this topic showing that ADT interferes on PCa at different levels that can be investigated by specific biological markers.
Minerva urologica e nefrologica = The Italian journal of urology and nephrology. 2018 Feb 01 [Epub ahead of print]
Alessandro Antonelli, Carlotta Palumbo, Alessandro Veccia, Salvatore Grisanti, Luca Triggiani, Stefania Zamboni, Maria Furlan, Claudio Simeone, Stefano Magrini, Alfredo Berruti
Urology Unit, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy - ., Urology Unit, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy., Medical Oncology Unit, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy., Radiation Oncology Unit, ASST Spedali Civili di Brescia, University of Brescia, Brescia, Italy.