Prostate cancer was the second most common incident cancer in men in 2020. Approximately 10-50% of cases develop metastatic castration-resistant prostate cancer (mCRPC).

This systematic review aimed to re-evaluate the evidence about the efficacy and safety of the 177Lutetium prostate-specific membrane antigen radioligand therapy (177Lu-PSMA-RLT) compared to standard care in adult males with PSMA-positive mCRPC.

Three randomised controlled trials (RCTs) were included for the evidence synthesis. The evidence of moderate certainty regarding overall survival indicates superiority of 177Lu-PSMA-617 in combination with standard care (without cytotoxic chemotherapy) versus standard care alone. In addition, the evidence shows a potential superiority of the 177Lu-PSMA-617 combination therapy for progression-free survival and health-related quality of life. However, the results should be interpreted with caution owing to the low certainty of the evidence for these outcomes.

Against this background, including 177Lu-PSMA-RLT combined with standard care (without cytotoxic chemotherapy) in the hospital benefit catalogue should be restricted to selected patients and limited to specialised centres. In addition, "self-synthesised" 177Lu-PSMA-RLTs of radiopharmaceutical units could be considered. A re-evaluation is recommended not before 2025 after further RCTs have been published.