Androgen receptor pathway inhibitors (ARPIs) as monotherapy are studied increasingly across prostate cancer disease states. We aimed to evaluate the safety, oncologic efficacy, and quality of life (QoL) of ARPI monotherapy as compared with ARPI + androgen deprivation therapy (ADT) and ADT alone.
PubMed/Medline, Embase, and Cochrane/Central were queried through June 2024 for clinical trials. The primary outcomes were the rates of adverse events (AEs) presented as risk ratios (RRs); the secondary outcomes included efficacy and QoL.
We synthesized data from 2015 men, retrieved from 17 studies. The incidence of any AEs was similar between patients on ARPIs, ARPI + ADT (RR: 1.01, 95% confidence interval [CI]: 1-1.02, p = 0.08), and ADT (RR: 1.01, 95% CI: 0.98-1.04, p = 0.3). The incidence of grade ≥3 AEs was higher in patients on ARPI monotherapy than in those on ADT (RR: 1.18, 95% CI: 1.11-1.24, p < 0.01), driven mainly by fatigue and cardiovascular toxicity. There was no statistically significant difference in grade ≥3 AEs between patients treated with ARPIs and ARPI + ADT (RR: 1.07, 95% CI: 0.87-1.3, p = 0.4). ARPI monotherapy led to a lower incidence of hot flushes (RR: 0.4, 95% CI: 0.18-0.89, p = 0.03) but higher incidences of breast pain (RR: 6.03, 95% CI: 3.34-10.88, p < 0.01) and gynecomastia (RR: 5.73, 95% CI: 3.79-8.66, p < 0.01) than treatment with ARPI + ADT. ARPIs demonstrated promising oncologic efficacy for patients with biochemical recurrence, while maintaining favorable overall and sexual QoL.
ARPI monotherapy results in overall similar toxicities for ARPI + ADT and ADT alone. The specific AE pattern of each combination can serve as a basis to tailor therapy to each patient's needs and wishes.
European urology focus. 2025 May 21 [Epub ahead of print]
Tamás Fazekas, Marcin Miszczyk, Alexander Giesen, Tamás Kói, Fabio Zattoni, Lara Rodriguez-Sanchez, Takafumi Yanagisawa, Akihiro Matsukawa, Tibor Szarvas, Piotr Kryst, Juan Gómez Rivas, Axel S Merseburger, Maria De Santis, Steven Joniau, Alberto Briganti, Giancarlo Marra, Péter Nyirády, Giorgio Gandaglia, Shahrokh F Shariat, Pawel Rajwa, EAU-YAU Prostate Cancer Working Group
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Collegium Medicum, Faculty of Medicine, WSB University, Dąbrowa Górnicza, Poland., Department of Urology, University Hospitals Leuven, Leuven, Belgium; Department of Development and Regeneration, KU Leuven, Leuven, Belgium., Centre for Translational Medicine, Semmelweis University, Budapest, Hungary; Department of Stochastics, Institute of Mathematics, Budapest University of Technology and Economics, Budapest, Hungary., Department of Surgery, Oncology, and Gastroenterology - Urology Clinic, University of Padua, Padua, Italy; Department of Medicine (DIMED), University of Padua, Padova, Italy., Department of Urology, Institut Mutualiste Montsouris, Paris, France., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Semmelweis University, Budapest, Hungary; Department of Urology, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, Essen, Germany., Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland., European Association of Urology Young Academic Urologists, Arnhem, The Netherlands; Department of Urology, Hospital Clinico San Carlos, Madrid, Spain., Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Charité Universitätsmedizin Berlin, Berlin, Germany., Vita-Salute San Raffaele University, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy., Division of Urology, Department of Surgical Sciences, Molinette Hospital, Città della Salute E della Scienza and University of Turin, Turin, Italy., Department of Urology, Semmelweis University, Budapest, Hungary; Centre for Translational Medicine, Semmelweis University, Budapest, Hungary., Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland; Vita-Salute San Raffaele University, Milan, Italy; Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czechia; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Research Centre for Evidence Medicine, Urology Department, Tabriz University of Medical Sciences, Tabriz, Iran; Hourani Center for Applied Scientific Research, Al-Ahliyya Amman University, Amman, Jordan. Electronic address: ., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Surgery and Interventional Science, University College London, London, UK; Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland.