Lutetium-PSMA therapy—a new therapeutic option in metastatic castration-resistant prostate cancer?

Although localized prostate cancer (PC) is a curable disease, a significant proportion of patients progress from advanced PC to metastatic castration-resistant prostate cancer (mCRPC). Several new treatments for mCRPC were approved including new hormonal therapies, chemotherapies, and radium-223. For patients with disease progression after the standard therapies, lutetium-prostate-specific membrane antigen (Lu-PSMA) therapy could be an option.

The aim of this short review is to give an overview of the available evidence of the efficacy and toxicity of Lu-PSMA therapy. To date, one prospective phase II trial and several small retrospective studies have been published including almost 400 patients. Primary endpoint of all available trials was a decline in PSA of >50%, which was achieved in 30–70% of men treated with Lu-PSMA therapy. A PSA decline was observed in 70–91% of cases. Overall survival was reported only in small retrospective subgroups, and no prospective data are available. Progressive disease was observed in 11–32% of patients after Lu-PSMA treatment.

Lu-PSMA treatment seems to be well tolerated and safe. One common treatment-related grade 1 adverse event is dry mouth in up to 87% of men after radioligand therapy (RLT). Therefore, in the vast majority no treatment is needed. Hematologic toxicity such as thrombocytopenia caused serious grade 3–4 adverse events in 27% of patients in the prospective trial. No immediate adverse events after radioligand infusion and no treatment-related deaths were reported.

According to preliminary data, Lu-PSMA therapy seems to be well tolerated and safe for progressive end-stage mCRPC patients. Further prospective trials are needed.