Case report: Exceptional and durable response to Radium-223 and suspension of androgen deprivation therapy in a metastatic castration-resistant prostate cancer patient.

Despite the development of new therapies in the last few years, metastatic prostate cancer (PCa) is still a lethal disease. Radium-223 (Ra-223) is approved for patients with advanced castration-resistant prostate cancer (CRPC) with bone metastases and no visceral disease. However, patients' outcomes are heterogenous, and there is lack of validated predictive biomarkers of response, while biomarkers for early identification of patients who benefit from treatment are limited. This case report describes a remarkable and durable response to Ra-223 in a CRPC patient with bone metastases who had rapidly progressed to many previous therapies; this response is now lasting for 5 years even after having stopped backbone androgen deprivation therapy (ADT). Here, we present the clinical course of this exceptional response, as well as comprehensive genomic and histopathology analyses on sequential biopsies acquired before and after therapy. Additionally, we review current knowledge on predictive and response biomarkers to Ra-223 in metastatic prostate cancer.

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Copyright © 2024 Zacchi, Carles, Gonzalez, Maldonado, Perez-Lopez, Semidey and Mateo.

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JM has served as an advisor for AstraZeneca, Amunix/Sanofi, Daichii-Sankyo, Janssen, MSD; Pfizer, Roche, and Nuage Therapeutics. He is PI for grants to institutions by AstraZeneca, Pfizer, and Amgen. JC received consulting and speaker’s fees from Bayer, Johnson & Johnson, Bristol-Myers Squibb, Astellas Pharma, Pfizer, Sanofi, MSD Oncology, Roche, AstraZeneca and Asofarma, and research support from AB Science, Aragon Pharmaceuticals, Arog Pharmaceuticals INC, Astellas Pharma., Astrazeneca AB, Aveo Pharmaceuticals INC, Bayer AG, Blueprint Medicines Corporation, BN Immunotherapeutics INC, Boehringer Ingelheim, Bristol-Myers Squibb International Corporation BMS, Clovis Oncology INC, Cougar Biotechnology INC, Deciphera Pharmaceuticals LLC, Exelixis INC, F. Hoffmann-La Roche LTD, Genentech INC, Glaxosmithkline, SA, Incyte Corporation, Janssen-Cilag International NV, Karyopharm Therapeutics INC, Laboratoires Leurquin Mediolanum SAS, Lilly SA, Medimmune, Millennium Pharmaceuticals INC., Nanobiotix SA, Novartis Farmacéutica SA, Pfizer, S.L.U, Puma Biotechnology INC, Sanofi-Aventis SA, SFJ Pharma LTD. II, Teva Pharma S.L.U. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.