Toxicities of radioligand and radioisotope therapy in prostate cancer: a systematic review and meta-analysis

Ventura D, Noto B, Jauregui NR, Roll W, Rahbar K

Abstract

Purpose of review: This systematic review and meta-analysis investigate the toxicities of radioligand and radioisotope therapies - [ 177 Lu]lutetium-prostate-specific membrane antigen (PSMA) (Lu-PSMA), [ 225 Ac]actinium-PSMA (Ac-PSMA), and [ 223 Ra]radium-dichloride (223-Radium) - in metastatic prostate cancer. While previous studies have explored this topic, most failed to differentiate between treatment-emergent adverse events (TEAEs) and preexisting conditions, leading to inflated toxicity rates. By focusing exclusively on TEAEs, this study provides a more accurate and clinically relevant assessment. Recent findings: This meta-analysis of 65 studies including 8706 patients identified haematotoxicities as the most frequent TEAEs across all therapies, affecting 10-20% of patients. Fatigue is a common nonhematologic adverse event in all treatments. Low grade xerostomia is specifically associated with Lu-PSMA and Ac-PSMA therapies, occurring in 30% and 84% of patients, respectively, while 223-Radium is uniquely linked to an increased fracture risk. Severe toxicities (Common Terminology Criteria for Adverse Events ≥ 3) are rare across all therapies. By clearly distinguishing TEAEs from baseline conditions, this study addresses a gap in the existing literature. Summary: Severe TEAEs are uncommon across Lu-PSMA, Ac-PSMA, and 223-Radium therapies. Still, monitoring and managing specific toxicities to optimize the safety and tolerability of these therapies in clinical practice is mandatory, especially concerning xerostomia in Ac-PSMA therapy.