Frequency and new-onset rates of nausea and fatigue in 177Lu-PSMA therapy with standardized premedication

Aim PSMA-based radioligand therapy (PSMA-RLT) for metastatic castration-resistant prostate cancer (mCRPC) is associated with nausea, vomiting, and fatigue. We evaluated whether standardized premedication with glucocorticoids and antiemetics reduces these side effects. Methods In this retrospective multicentre study, 67 mCRPC patients received 322 cycles of 177 Lu-PSMA-617 at three Swiss centres. All patients received 8 mg dexamethasone and 8 mg ondansetron intravenously 30 minutes before therapy. Side effects were assessed using study-specific questionnaires (195/322 returned; 61%). Baseline symptoms were documented using EORTC questionnaires in 30 patients. Biochemical response was evaluated in 36 patients using PCWG3 criteria. Results Absolute side effect rates were: nausea within 3 days 20.9%, inter-cycle nausea 35.8%, vomiting 10.4%, and fatigue 67.2%. After correction for baseline symptoms, estimated new-onset rates were lower: 16.3%, 26.1%, 7.0%, and 6.7%, respectively. Early nausea significantly predicted inter-cycle nausea (p=0.02). Side effects followed a U-shaped pattern across cycles. No significant association was observed between side effects and PCWG3 biochemical response, though statistical power was limited. Conclusions Absolute rates of nausea and fatigue were comparable to the VISION trial. However, new-onset rates of these two side effects were substantially lower after accounting for baseline symptoms. A protective effect of premedication with glucocorticoids and antiemetics could be the reason for this, but requires confirmation in prospective controlled studies.