Targeted radionuclide therapies for prostate cancer: clinical insights and innovation

Summary Treatment options for prostate cancer (PCa) are diverse and depend on the stage of the disease. Surgical radical prostatectomy or local radiation therapies, including external beam radiation and brachytherapy, remain standard approaches for localized clinically significant PCa. In cases of tumor recurrence or metastasis, conventional systemic treatments such as androgen deprivation therapy (ADT) or chemotherapy are generally effective but often associated with considerable side effects and, in many patients, suboptimal response rates. Consequently, radionuclide therapies have gained increasing importance in clinical practice. These treatments target-specific receptors and frequently achieve comparable or improved therapeutic outcomes with a more favorable side-effect profile. [ 223 Radium]Ra-dichloride was the first radionuclide therapy approved by the U.S. Food and Drug Administration (FDA) for PCa in May 2013, followed by [ 177 Lutetium]Lu labeled prostate-specific membrane antigen (PSMA) in March 2022. More recently, novel radioligand therapies such as [ 225 Actinium]Ac-PSMA, potentially beneficial in metastases resistant to beta-emitters, and [ 161 Terbium]Tb-PSMA, designed to target micrometastases undetectable by PSMA-targeted positron-emission tomography/computed tomography (PET/CT), have been developed. Ongoing studies are investigating combinations of these radionuclide therapies with each other or with systemic treatments such as ADT, chemotherapy, or poly(ADP-ribose) polymerase inhibitors, which may help to fully explore and realize the potential of these innovative approaches.