Combination systemic therapies have become the standard for metastatic hormone-sensitive prostate cancer (mHSPC). However, the effect of age on oncologic outcomes remains unknown. Our aim was to perform a systematic review, meta-analysis, and network meta-analysis (NMA) on the effect of chronological age on overall survival (OS) in patients treated with combination therapies for mHSPC.
We searched the PubMed®, Web of ScienceTM, and Scopus® databases to identify randomized controlled trials (RCTs) that analyzed the efficacy of combination systemic therapies using ADT plus docetaxel and/or androgen receptor signaling inhibitor (ARSI) in patients with mHSPC. We included studies, which provided separate hazard ratios (HRs) for younger vs. older patients. The selected age cut-off was 70 years (±5 years). Our outcome of interest was OS.
We included nine RCTs with a total of 9183 patients. Younger and older men constituted 51% and 49% of included patients, respectively. Docetaxel plus ADT significantly improved OS among both older (HR 0.79, 95% CI 0.63-0.99, p = 0.04) and younger patients (HR 0.79, 95% CI 0.69-0.90, p < 0.001) with no differences according to age. ARSI plus ADT improved OS in older (HR 0.72, 95% CI 0.64-0.80, p < 0.001) and younger (HR 0.58, 95% CI 0.51-0.66, p < 0.001) patients; younger patients did benefit more (p = 0.02). On NMA treatment ranking, triplet therapy showed the highest probability of OS benefit irrespective of age group; in older patients, the benefit of triplet therapy compared to doublet was less expressed.
Patients with mHSPC benefit from combination systemic therapies irrespective of age; the effect is, however, more evident in younger patients. Chronological age alone seems not to be a selection criteria for the administration of combination systemic therapies.
Prostate cancer and prostatic diseases. 2022 Oct 25 [Epub ahead of print]
Pawel Rajwa, Takafumi Yanagisawa, Isabel Heidegger, Fabio Zattoni, Giancarlo Marra, Timo F W Soeterik, Roderick C N van den Bergh, Massimo Valerio, Francesco Ceci, Claudia V Kesch, Veeru Kasivisvanathan, Ekaterina Laukhtina, Tatsushi Kawada, Peter Nyiriadi, Quoc-Dien Trinh, Piotr Chlosta, Pierre I Karakiewicz, Guillaume Ploussard, Alberto Briganti, Francesco Montorsi, Shahrokh F Shariat, Giorgio Gandaglia, EAU-YAU Prostate Cancer Working Party
Department of Urology, Medical University of Vienna, Vienna, Austria., Department of Urology, Medical University Innsbruck, Innsbruck, Austria., Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy., Department of Urology, San Giovanni Battista Hospital, University of Torino, Torino, Italy., Department of Urology, St Antonius Hospital, Utrecht, The Netherlands., Department of Urology, CHUV Lausanne, Lausanne, Switzerland., Division of Nuclear Medicine, European Institute of Oncology IRCCS, Milan, Italy., Department of Urology, University Hospital Essen, Essen German Cancer Consortium (DKTK) University Hospital Essen, Essen, Germany., Division of Surgery and Interventional Science, University College London, London, UK., Department of Urology, Semmelweis University, Budapest, Hungary., Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA., Department of Urology, Jagiellonian University, Krakow, Poland., Cancer Prognostics and Health Outcomes Unit, Division of Urology, University of Montreal Health Center, Montreal, QC, Canada., Department of Urology, La Croix du Sud Hospital, Quint Fonsegrives, France., Unit of Urology/Division of Oncology, IRCCS San Raffaele, San Raffaele Hospital, Milan, Italy., Department of Urology, Medical University of Vienna, Vienna, Austria. .