Top advances of the year: Radiopharmaceutical therapy for prostate cancer

Abstract Radiopharmaceutical therapy, a form of targeted radionuclide therapy, has emerged as a rapidly advancing area in prostate cancer management, with significant developments in 2025. The field, which began to transform from pain palliation to cancer‐directed end points with the α‐emitting agent radium‐223 for bone‐predominant metastatic androgen pathway modulator resistant (mAPMR) disease, expanded considerably following the introduction of prostate‐specific membrane antigen targeted imaging and therapy. The approval of 177 Lu‐PSMA‐617 in 2022 opened the door to exploring its benefit across the disease continuum and in combination with contemporary systemic and local treatments, with the goal of improving survival while maintaining safety. The year 2025 produced some of the most impactful advances to date. In the mAPMR setting, regulatory approval of 177 Lu‐PSMA‐617 was extended into the pre‐chemotherapy state based on the PSMAfore trial. Also, in mAPMR disease, the PEACE‐3 trial established the combination of radium‐223 with enzalutamide as an option when bone protective agents are used. Beyond the resistant setting, radiopharmaceuticals are being evaluated as treatment‐intensification strategies earlier in the disease course. In the metastatic APM naive or sensitive (APMN/S) setting, the PSMAddition trial demonstrated that adding 177 Lu‐PSMA‐617 to standard hormonal therapy delays disease progression. In the oligorecurrent APMN/S setting, the LUNAR trial showed that using PSMA‐targeted radionuclide therapy before stereotactic body radiotherapy improves progression‐free outcomes, suggesting a role for targeting small‐volume metastatic disease in patients deferring hormonal therapy. Together, these developments represent the top advances of the year and reflect a rapidly evolving and increasingly promising field of radiopharmaceutical therapy in prostate cancer.