PMID- 34169003 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220424 IS - 2234-943X (Print) IS - 2234-943X (Electronic) IS - 2234-943X (Linking) VI - 11 DP - 2021 TI - A Systematic Review and Meta-Analysis of Randomized Controlled Trials With Novel Hormonal Therapies for Non-Metastatic Castration-Resistant Prostate Cancer: An Update From Mature Overall Survival Data. PG - 700258 LID - 10.3389/fonc.2021.700258 [doi] LID - 700258 AB - INTRODUCTION: To get better insight into the management of non-metastatic castration-resistant prostate cancer (M0 CRPC), in this meta-analysis and review we aimed to present an updated evaluation of the efficacy and safety of novel hormonal therapies (nHT) for M0 CRPC according to final analyses with mature overall survival (OS) and safety data. METHODS: We analyzed metastasis-free survival (MFS), OS, time to prostate-specific antigen (PSA) progression, second-line therapies data, adverse events (AEs), including all AEs, serious AEs (SAEs), AEs leading to discontinuation of trial regimen, AEs leading to death, fatigue, dizziness, cardiovascular events, and fractures; moreover, we evaluated the impact of PSA doubling time (PSA-DT), Eastern Cooperative Oncology Group (ECOG) score, use of bone-targeted therapy, lymph lodes (LN) status, and prior HT on final OS data. A comparison among the placebo arms of the included trials in terms of survival and safety profiles was assessed. RESULTS: According to the pooled analysis with updated and mature OS data, OS was significantly improved with nHT compared to placebo (hazard ratio (HR)= 0.74, 95% confidence interval (CI)= 0.66-0.84). nHT significantly improved OS over placebo across all pre-specified subgroups. Subgroup analysis revealed a greater OS benefit in patients with PSA-DT >6 months than /=2); yet, differences between pre-specified subgroups were not significant (all p> 0.05). Overall, the nHT arm was significantly associated with higher rates of AEs, when compared with the placebo arm. The long-term analysis showed a worse safety profile with nHT than the interim analysis. CONCLUSIONS: According to final analyses, nHT have shown to improve OS over placebo in the setting of high-risk M0 CRPC. The long-term analysis showed a worse safety profile with nHT than the interim analysis, whit distinct profiles among different nHT. The lack of survival data regarding second-line therapies remains a major issue. CI - Copyright (c) 2021 Maggi, Salciccia, Del Giudice, Busetto, Falagario, Carrieri, Ferro, Porreca, Di Pierro, Fasulo, Frantellizzi, De Vincentis, De Berardinis and Sciarra. FAU - Maggi, Martina AU - Maggi M AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - Salciccia, Stefano AU - Salciccia S AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - Del Giudice, Francesco AU - Del Giudice F AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - Busetto, Gian Maria AU - Busetto GM AD - Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy. FAU - Falagario, Ugo G AU - Falagario UG AD - Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy. FAU - Carrieri, Giuseppe AU - Carrieri G AD - Department of Urology and Renal Transplantation, University of Foggia, Policlinico Riuniti, Foggia, Italy. FAU - Ferro, Matteo AU - Ferro M AD - Department of Urology, European Institute of Oncology (IEO), Milan, Italy. FAU - Porreca, Angelo AU - Porreca A AD - Department of Urology, Veneto Institute of Oncology (IOV) IRCCS, Padua, Italy. FAU - Di Pierro, Giovanni Battista AU - Di Pierro GB AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - Fasulo, Vittorio AU - Fasulo V AD - Department of Urology, Istituto Clinico Humanitas IRCCS-Clinical and Research Hospital, Milan, Rozzano, Italy. FAU - Frantellizzi, Viviana AU - Frantellizzi V AD - Department Of Maternal-Infant And Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - De Vincentis, Giuseppe AU - De Vincentis G AD - Department Of Maternal-Infant And Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - De Berardinis, Ettore AU - De Berardinis E AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. FAU - Sciarra, Alessandro AU - Sciarra A AD - Department of Maternal-Infant and Urological Sciences, Sapienza Rome University, Policlinico Umberto I, Rome, Italy. LA - eng PT - Systematic Review DEP - 20210608 PL - Switzerland TA - Front Oncol JT - Frontiers in oncology JID - 101568867 PMC - PMC8217817 OTO - NOTNLM OT - adverse events OT - hormonal therapy OT - metastasis OT - non-metastatic castration-resistant prostate cancer OT - overall survival OT - prostate neoplasm COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/06/26 06:00 MHDA- 2021/06/26 06:01 PMCR- 2021/01/01 CRDT- 2021/06/25 06:53 PHST- 2021/04/25 00:00 [received] PHST- 2021/05/14 00:00 [accepted] PHST- 2021/06/25 06:53 [entrez] PHST- 2021/06/26 06:00 [pubmed] PHST- 2021/06/26 06:01 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fonc.2021.700258 [doi] PST - epublish SO - Front Oncol. 2021 Jun 8;11:700258. doi: 10.3389/fonc.2021.700258. eCollection 2021.