A Treatment Paradigm Shift: Targeted Radionuclide Therapies for Metastatic Castrate Resistant Prostate Cancer

SIMPLE SUMMARY: Metastatic prostate cancer has traditionally been treated with a combination of hormonal and chemotherapy regimens. With the recent FDA approval of targeted radionuclide therapeutics, there is now a new class of therapy that is routinely available to patients and clinicians. This review explores the most commonly studied therapeutic radiopharmaceuticals and their appropriate use and contraindications. Additionally, we detail how these therapeutic radiopharmaceuticals can fit into the common medical oncology practice and future directions of this field of medicine. ABSTRACT: The recent approval of (177)Lu PSMA-617 (Pluvicto(®)) by the United States Food and Drug Administration (FDA) is the culmination of decades of work in advancing the field of targeted radionuclide therapy for metastatic prostate cancer. (177)Lu PSMA-617, along with the bone specific radiotherapeutic agent, (223)RaCl(2) (Xofigo(®)), are now commonly used in routine clinical care as a tertiary line of therapy for men with metastatic castrate resistant prostate cancer and for osseus metastatic disease respectively. While these radiopharmaceuticals are changing how metastatic prostate cancer is classified and treated, there is relatively little guidance to the practitioner and patient as to how best utilize these therapies, especially in conjunction with other more well-established regimens including hormonal, immunologic, and chemotherapeutic agents. This review article will go into detail about the mechanism and effectiveness of these radiopharmaceuticals and less well-known classes of targeted radionuclide radiopharmaceuticals including alpha emitting prostate specific membrane antigen (PSMA)-, gastrin-releasing peptide receptor (GRPR)-, and somatostatin targeted radionuclide therapeutics. Additionally, a thorough discussion of the clinical approach of these agents is included and required futures studies.