Xofigo (radium Ra-223 dichloride)

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

Promising results have led to the approval of several PARPi agents as monotherapy or in combination with ARPIs in selected or unselected patients when chemotherapy is not clinically indicated. However, some questions remain regarding patient selection and treatment sequencing.

P=N/A, N=38, Not yet recruiting, Washington University School of Medicine

The combination of 177Lu-PSMA-I&T and 223Ra is safe and feasible in patients with metastatic castration-resistant prostate cancer and bone metastases. These findings warrant further evaluation of combined α-emitting and β-emitting approaches.

As the majority of men with metastatic castration-resistant prostate cancer first present with bone-only metastases, they may be treated initially with radium-223, while still remaining eligible to benefit from chemotherapy and 177Lu-PSMA upon subsequent progression of skeletal metastatic disease and/or the emergence of lymph node or visceral metastases. Graphical abstract available for this article.

P1, N=43, Completed, Tufts Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2026 --> Sep 2025

P1, N=46, Completed, Bayer | Active, not recruiting --> Completed

P2, N=30, Active, not recruiting, University of Southern California | Trial completion date: Nov 2025 --> Nov 2027 | Trial primary completion date: Nov 2024 --> Nov 2026

These include androgen receptor signaling inhibitors such as enzalutamide and abiraterone acetate, taxane-based chemotherapies including docetaxel and cabazitaxel, and bone-targeting radiopharmaceuticals like radium-223. Immunotherapeutic agents have also contributed to expanding treatment options with Sipuleucel-T, a dendritic cell-based vaccine, and pembrolizumab, a PD-1 immune checkpoint inhibitor approved for select patient populations. Furthermore, the introduction of poly (ADP-ribose) polymerase inhibitors like olaparib and rucaparib, has transformed the therapeutic landscape, particularly for patients with DNA repair deficiencies in metastatic prostate cancer...In this review, we highlight adoptive cellular therapies utilizing CAR-T cells engineered to recognize prostate cancer-specific antigens, aiming to overcome immune evasion mechanisms. We summarize current CAR-T modalities with their limitations and prospects being evaluated in both preclinical and clinical settings of metastatic prostate cancer.

In conclusion, α‑radiation induced distinct proteomic, lipidomic and miRNA changes in OBCs, potentially affecting BM radiosensitivity. These molecules may serve as candidate biomarkers for predicting individual susceptibility to α‑emitting radionuclide therapy.

Clinical efforts to combine targeted radiation with synthetic lethality approaches are ongoing. Tailoring radiopharmaceutical therapy to individual tumor DNA repair profiles offers a promising paradigm to improve outcomes and expand therapeutic windows in advanced prostate cancer.

Despite the small size, these findings suggest that patient with HRD may have a slight improvement in survival outcomes after 223Ra treatment, but prospective validation is required.