Nuclear Medicine and External Beam Radiation Therapy in Prostate Cancer: A Synergistic Approach.

Radiopharmaceutical therapy (RPT) combined with external beam radiotherapy (EBRT) is emerging as a powerful approach in prostate cancer treatment. Historically rooted in early Sr trials, this combination leverages EBRT's precise targeting of visible tumors and RPT's ability to address microscopic or systemic disease. Clinical and preclinical evidence shows enhanced tumor control, improved pain relief, and improved quality of life with manageable toxicity. Advanced imaging-particularly prostate-specific membrane antigen (PSMA) PET-plays a pivotal role in precise disease mapping, patient selection, and therapeutic planning. PSMA-targeted RPT, including Lu-PSMA, expands the arsenal by delivering systemic radiation to PSMA-expressing cancer cells, with demonstrated overall survival benefits so far primarily in metastatic castration-resistant prostate cancer after androgen receptor pathway inhibitors and taxane therapies. Although practical challenges such as access, regulation, and dosimetry remain, ongoing trials are exploring concurrent and sequential strategies, including α-emitter radioligands, aiming to improve survival. As evidence accumulates and logistical barriers are addressed, combined RPT and EBRT is poised to become a standard, personalized treatment paradigm in prostate cancer care.