Lutetium-177-PSMA in therapy of metastatic prostate cancer

Despite advances in the care of patients with metastatic castration-resistant prostate cancer (mCRPC), only 30% of them survive five years. Therefore, newer targeted therapeutic approaches are still being sought to prolong the survival of patients with mCRPC. More than 80% of prostate cancers over express prostate specific membrane antigen (PSMA), a transmembrane protein that is used as a molecular target for both imaging and therapy. In this work we focus on newer radioligand treatment, where a ligand, an inhibitor of PSMA protein is radiolabeled with mixed beta-gamma emitter - radioactive lutetium (177-Lu) - 177-Lu-PSMA. It is a small molecule that binds to metastatic prostate cancer cells that over express PSMA, unlike most normal tissues, and irradiates them to cause damage of the irradiated tumor cells. Treatment with 177-Lu-PSMA yielded promising results in a recent prospective randomized open-label international study, VISION. This is the first study to demonstrate a significant improvement of overall survival in patients with progressive mCRPC treated with 177-Lu-PSMA-617 and pretreated with at least one of the second-generation hormone therapy - androgen receptor targeted agents (ARTA) and chemotherapy. Currently, 177-Lu-PSMA is indicated for the treatment of men with mCRPC previously treated with docetaxel and concomitantly with abiraterone or enzalutamide. (author)