The therapeutic use of 177 Lu-PSMA-617 radioligand therapy in prostate cancer treatment: a review of literature and ongoing trials.

Radioligand therapy is a targeted cancer treatment modality in which radioisotopes are utilized in the delivery of radiation at targeted cancer cells, with the goal of sparing normal cells. Prostate cancer is a well-known radiosensitive disease, historically treated with radioisotopes such as Strontium-89, Samarium-153, and Radium-223 for palliation of bone metastases. Recently, prostate specific membrane antigen (PSMA) has recently been employed as a radioligand target due to its unique properties of high expression on the surface of prostate cancer cells, limited expression in normal tissue, function as an internalizing cell surface receptor, and increased expression with androgen deprivation therapy. In 2015, Lu-PSMA-617 was first introduced as a promising treatment option for castration-resistant prostate cancer, and 7 years later the results of the phase III VISION trial led to Lu-PSMA-617 gaining FDA approval for the treatment of progressive castration-resistant prostate cancer. These results in combination with the inherent properties of Lu-PSMA-617 have led to its current exploration as a promising treatment modality beyond progressive metastatic castration-resistant prostate cancer, and into the earlier phases of prostate cancer. This review paper aims to highlight the key phase III randomized controlled trials related to Lu-PSMA-617 in all stages of prostate cancer, as well as bring attention to ongoing, earlier phase I/II trials incorporating Lu-PSMA-617.