For patients with advanced prostate cancer (PC) treated with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI), the decline in prostate-specific antigen (PSA) is a potential biomarker for treatment response.
We synthesised data regarding the association of the PSA response with overall survival (OS).
The MEDLINE, Embase, Web of Science, and Google Scholar databases were searched up to November 2024 to identify studies evaluating the association between the PSA response and OS among patients treated with ADT + ARPI. Hazard ratios (HRs) were pooled in random-effects meta-analyses.
We identified 14 studies comprising a total of 8883 patients. Among four studies in metastatic hormone-sensitive PC (n = 2197), achievement of an undetectable PSA level was associated with better OS (HR 0.33, 95% confidence interval [CI] 0.23-0.49). In two studies in nonmetastatic castration-resistant PC (n = 1507), a PSA decline to <0.2 ng/ml (HR 0.28, 95% CI 0.21-0.36), a PSA reduction of ≥90% (HR 0.39, 95% CI 0.28-0.52), and a PSA reduction of ≥50% (HR 0.34, 95% CI 0.16-0.69) were associated with better OS. Among four studies in metastatic castration-resistant PC (n = 3728), PSA reductions of ≥90% (HR 0.22, 95% CI 0.14-0.34) and ≥50% (HR 0.29, 95% CI 0.20-0.41) were associated with better OS. The main limitations include heterogeneity in study designs and use of ADT before baseline PSA measurement in mHSPC studies.
The PSA response following ADT + ARPI therapy is significantly associated with OS across all metastatic and castration-resistant PC states and could serve as a clinically useful early signal of efficacy. It remains to be proven whether the PSA response is a surrogate for OS or should guide changes in clinical care.
European urology focus. 2025 May 15 [Epub ahead of print]
Marcin Miszczyk, Tamás Fazekas, Paweł Rajwa, Akihiro Matsukawa, Ichiro Tsuboi, Michael S Leapman, Gero Kramer, Maha Hussain, Axel Merseburger, Alberto Briganti, Anthony V D'Amico, Silke Gillessen, Fred Saad, Shahrokh F Shariat
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, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Semmelweis University, Budapest, Hungary., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Division of Surgery and Interventional Sciences, University College London, London, UK; Second Department of Urology, Centre of Postgraduate Medical Education, Warsaw, Poland., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan., Department of Urology, Yale University School of Medicine, New Haven, CT, USA., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Department of Urology, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany., Unit of Urology/Division of Oncology, Urological Research Institute, IRCCS Ospedale San Raffaele, Vita-Salute San Raffaele University, Milan, Italy., Department of Radiation Oncology, Brigham and Women's Hospital, Boston, MA, USA., Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland; Faculty of Biosciences, Università della Svizzera Italiana, Lugano, Switzerland., Department of Surgery/Urology, Centre Hospitalier de l'Université de Montréal, University of Montreal, Montreal, Canada., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czechia; Division of Urology, Department of Special Surgery, University of Jordan, Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Research Centre for Evidence Medicine, Urology Department, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40379533