Radiopharmaceuticals have been utilized for men with advanced
prostate cancer for decades. Older agents, seldom used today, provided palliation for bone metastatic
pain. In 2013, the alpha emitter
radium-223 provided a catalyst for the field by prolonging survival in men with metastatic castrate-resistant
prostate cancer (mCRPC). Recently radioisotopic
therapies have gained further interest with the development and FDA approval of 177
lutetium (177Lu)-PSMA-617 (also known as
lutetium Lu-177 vipivotide
tetraxetan). This agent targets the prostate-specific membrane
antigen (PSMA) expressed on the cell surface of
prostate cancer cells with a beta-emitting
isotope (177Lu). This clinical review summarizes key data reported from
177Lu-PSMA-617 clinical trials, including data from the phase III VISION trial which were pivotal for regulatory approval in heavily pretreated PSMA-PET-positive patients with mCRPC. The current field of
radiopharmaceuticals is in a rapid state of flux. Additional phase III trials are now ongoing in patients with mCRPC and in patients with metastatic castrate-sensitive
prostate cancer. The results from these potential practice-changing trials are highly anticipated. Earlier phase trials (I/II) are in progress examining combination
therapies, radiolabeled
monoclonal antibodies, and novel compounds. Studies of PSMA-targeted
therapies using both beta emitters such as 177Lu and novel alpha emitters such 225
actinium are in progress. During the next decade,
radiopharmaceuticals will likely play a central role in the management of patients with advanced
prostate cancer.