The Role of Theranostics in Prostate Cancer

Theranostics in men with metastatic castration-resistant prostate cancer (mCRPC) has been developed to target bone and the tumor itself. Currently, bone-directed targeted alpha therapy with radium-223 (Ra-223) is the only theranostic agent proven to prolong survival in men with mCRPC who have symptomatic bone metastases and no known visceral metastases. The clinical utility and therapeutic success of Ra-223 has encouraged the development of other tumor-targeting theranostic agents in mCRPC, primarily targeting prostate-specific membrane antigen (PSMA) with radioligand therapy (RLT). There is increasing evidence of promising response rates and a low toxicity profile with Lu-177-labeled PSMA RLT in patients with mCRPC. A phase III randomized study of Lu-177-labeled PSMA RLT has completed accrual and is awaiting results as to whether the drug improves radiographic progression free survival and overall survival in men with mCRPC receiving standard of care treatments. Additional early clinical trials are investigating the role of tumor-directed targeted alpha therapy with radiotracers such as Ac-225. In this article, we review the current status of theranostics in prostate cancer, discussing the challenges and opportunities of combination therapies with more conventional agents such as androgen receptor inhibitors, cytotoxic chemotherapy, and immunotherapy. (C) 2020 Published by Elsevier Inc.