Current state of theranostics in metastatic castrate‐resistant prostate cancer

Abstract

SummaryProstate cancer remains one of the leading causes of cancer‐related death in the world. There have been significant advances in chemotherapy, hormonal therapy and targeted therapy options for patients with castrate‐resistant disease. However, these systemic treatments are often associated with unwanted toxicities. Targeted therapy with radiopharmaceuticals has become of key interest to limit systemic toxicity and provides a more precision oncology approach to treatment. Strontium‐89, Samarium‐153 EDTMP and Radium‐223 have been trialled with mixed results. Strontium‐89 and Samarium‐153 EDTMP have shown benefits in palliating metastatic bone pain but with no impact on survival outcomes. Early therapeutic radiopharmaceuticals targeting PSMA that were developed were beta‐emitting agents, but recently alpha‐emitting agents are being investigated as potentially superior options. Radium‐223 is the first alpha‐particle emitter therapeutic agent approved by the FDA, with phase III trial evidence showing benefits in overall survival and delay in symptomatic skeletal events for patients. Recently, 177‐Lutetium‐PSMA‐617 has demonstrated significant survival advantages in pre‐treated metastatic castrate‐resistant cancer patients in a number of phase II and III studies. Furthermore, 225‐Actinium‐PSMA‐617 also showed promise even in patients pre‐treated with 177‐Lutetium‐PSMA‐617. Hence, there has been an explosion of radiopharmaceutical treatment options for patients with prostate cancer. This review explores past and current theranostic capacities in the radiopharmaceutical treatment of metastatic castrate‐resistant prostate cancer.