Baseline PSMA-ligand PET/CT as a predictive biomarker for early progression in metastatic castration-resistant prostate cancer patients undergoing [177Lu]Lu-PSMA-617 radioligand therapy.

Abstract

ObjectiveTo identify predictive biomarkers of early progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (RLT).MethodsThis retrospective single-center study included all consecutive mCRPC patients who initiated [¹⁷⁷Lu]Lu-PSMA-617 RLT outside of clinical trials between July 2022 and May 2025, receiving at least 2 injections, and had a minimum follow-up period of 6 months. Early progression was defined as treatment discontinuation due to progression before the third injection or biochemical progression based on Prostate Cancer Working Group 3 without treatment discontinuation. Baseline clinical data, biological data, PSMA-ligand PET/CT and [¹⁸F]FDG PET/CT parameters were collected. Univariate and multivariate logistic regression were used to identify factors associated with early progression.ResultsA total of 87 patients were included. Early progression was observed in 27 (31%) of patients. Among baseline data, only a prior second-line chemotherapy with cabazitaxel and PSMA-ligand SUVmean ConclusionsPSMA-ligand SUVmean is an independent predictor of early progression confirming that baseline PSMA-ligand PET/CT may serve for risk stratification in mCRPC treated with [¹⁷⁷Lu]Lu-PSMA-617 RLT.