Xofigo (radium Ra-223 dichloride)

Subsequent radium-223 therapy further reduced bone metastases and normalized ALP levels, leading to substantial functional recovery. Furthermore, the favorable response to EP highlights the potential role of platinum-based chemotherapy in managing low-PSA, high-grade PC. Additional cases are needed to refine the clinical characterization of AVPC and establish evidence-based treatment guidelines.

P=N/A, N=38, Not yet recruiting, Washington University School of Medicine | Trial completion date: Nov 2027 --> Mar 2028 | Initiation date: Nov 2025 --> Mar 2026 | Trial primary completion date: Aug 2027 --> Dec 2027

P2, N=19, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=2, Active, not recruiting, University of California, San Francisco | Recruiting --> Active, not recruiting | N=54 --> 2 | Trial completion date: May 2028 --> Mar 2027 | Trial primary completion date: May 2026 --> Jan 2026

P3, N=732, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting

Transcriptomics reveals activation of DNA-damage response, immunogenic cell death, and antigen-presentation pathways, flow cytometry and immunohistochemistry show increased dendritic-cell maturation and CD8⁺ T-cell infiltration. Collectively, 223Ra/Ca-ALG MS demonstrates hypoxia-tolerant cytotoxicity, immune-activating potential, offering new insights for the development of immune-based TARE strategies in HCC and showing promising prospects for clinical translation.

In this study, the authors evaluated the distribution of thorium-227 (227Th) and its first daughter nuclide, radium-223 (223Ra), by analyzing tissue activity data from monkey studies from different antibody-based targeted thorium conjugates (hereafter called "conjugates")...The observation in monkeys that physical decay is the main elimination path for 227Th and that 223Ra undergoes a fast additional elimination in a typical tissue was consistent with clinical whole-body radioactivity data. The overarching consistency of the findings regarding tissue redistribution of 227Th and 223Ra across different conjugates and the consistency with clinical observations of whole body radioactivity in patients emphasize the importance of considering the potential redistribution of long-lived daughter nuclides of radionuclides used in therapeutic applications in humans.

The changes in tumor cell numbers after Ra223 treatment seemed to be inversely correlated with changes in CD3+/CD8+ and CD4+/FoxP3+ cells, but not with other immune cells, in these 3 patients. Further characterization of immune cells in the bone-TME will be required before developing strategies to enhance immunotherapy efficacy in bmCRPC.

P2, N=134, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P2, N=64, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Jul 2025 | Trial primary completion date: Dec 2026 --> Jul 2025

We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer.

P1, N=39, Active, not recruiting, University of Utah | Trial primary completion date: Jul 2025 --> Feb 2025