(177)Lu-PSMA Therapy for Metastatic Castration-Resistant Prostate Cancer: A Mini-Review of State-of-the-Art

BACKGROUND: Prostate specific membrane antigen (PSMA) ligand labeled with Lutetium-177 (177Lu) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). Several prospective and retrospective studies as well as clinical trials are completed or underway. This has ultimately led to the approval of this therapy by the US Food and Drug Administration (FDA) on March 23 2022. Our work aims to present a mini-review of the most recent research performed and the potential future directions of 177Lu-PSMA-radioligand therapy (RLT) for mCRPC patients. MAIN BODY: For patients with mCRPCwho have met the eligibility criteria for 177Lu-PSMA RLT, numerous studies and trials are either ongoing or have been completed. The studies included in this review have reported overall biochemical response, defined as a prostate-specific antigen (PSA) decline of at least 50%, in at least 44% of patients with mCRPC. The median ranges of overall survival (OS) and radiographic progression-free survival (rPFS) were reported within 10.7-56 and 3.6-16 months, respectively. With data from several retrospective and prospective studies published, the safety of 177Lu-PSMA RLT in mCRPC has been confirmed and demonstrated by its low toxicity profile. Various studies have published pharmacokinetic/pharmacodynamic models to better understand the absorption, distribution, metabolism, and excretion of the RLT in this patient population. Findings have been published for 177Lu-PSMA RLT alone and in combination with other agents. We summarize their findings in our review. CONCLUSIONS: The efficacy of 177Lu-PSMA RLT for patients with mCRPC has been proven thus far with promising results: PSA response, OS and rPFS when used alone or in combination with other treatment options, relative to the standard treatment options alone. The low toxicity profile noted also proves the safety of 177Lu-PSMA RLT in these patients.