Unlocking New Therapeutic Strategies in Oligometastatic Prostate Cancer with Radioligand and Metastasis-directed Radiation Therapy.

By delivering targeted radiation to tumor cells with a minimal impact on healthy tissues, radioligand therapy (RLT) has become an established treatment for metastatic castration-resistant prostate cancer. Its combination with external beam radiotherapy (EBRT) offers potential synergy: EBRT achieves high-dose, conformal local irradiation, whereas RLT can target systemic disease. This complementary approach could delay disease progression and improve local control, particularly in the oligometastatic setting. Emerging evidence supports the feasibility and safety of this approach, but prospective data remain limited. We summarize the current clinical landscape for this setting and pivotal ongoing trials investigating RLT + EBRT combinations for metachronous oligometastatic hormone-sensitive prostate cancer, with a focus on rationale, treatment sequencing, and future directions. Patient summary: In metastatic prostate cancer, the disease may spread to only a few sites in some cases, which is called oligometastatic prostate cancer (omPC). We describe a combined treatment strategy for patients with omPC. Radiotherapy targets tumors in specific areas, while radioligand therapy (which involves injection of a radioactive drug) can reach cancer cells throughout the body. Combining these two treatments may improve cancer control for both the primary tumor and metastases.