SPECIAL COMMENTARIESProstate-specific membrane antigen-targeted endoradiotherapy in metastatic prostate cancerLawal, Ismaheel O.a; Bruchertseifer, Frankb; Vorster, Marizab; Morgenstern, Alfreda,b; Sathekge, Mike M.aAuthor Information aDepartment of Nuclear Medicine, University of Pretoria, Pretoria, South Africa bEuropean Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany Correspondence to Mike M. Sathekge, MD, Ph.D., Department of Nuclear Medicine, University of Pretoria, Pretoria 0001, South Africa. Tel.: +27 12 354 1794;. e-mail: email@example.com Current Opinion in Urology: January 2020 - Volume 30 - Issue 1 - p 98-105 doi: 10.1097/MOU.0000000000000685 Buy Metrics Abstract Purpose of review In this review, we present an update on the safety and efficacy of prostate-specific membrane antigen (PSMA) radioligand therapy (PRLT) of metastatic castration-resistant prostate cancer (mCRPC). Recent findings Treatment of mCRPC with approved treatment agents leads to a survival advantage. The disease often progresses despite these treatments. PRLT with Lutetium-177 and Actinium-225 labeled with PSMA (LuPSMA and AcPSMA) have recently been shown to be effective and well tolerated for mCRPC treatment. LuPSMA is currently applied in patients who have exhausted approved treatment options or in whom these approved treatments are contraindicated. In this category of heavily pretreated patients, prostate-specific antigen (PSA) response (≥50% decline) is achieved in about 46% of patients. Side-effects are tolerable with rare reports of grade III–IV treatment-induced toxicity. AcPSMA is currently applied on a smaller scale in patients who relapsed after LuPSMA or in whom LuPSMA is contraindicated. PSA response occurs in up to 88% of patients treated with AcPSMA. Summary PRLT with LuPSMA and AcPSMA is a well-tolerated and effective treatment modality for mCRPC. Prospective randomized control trials are necessary to facilitate its application as an approved therapy option. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.