To identify predictive biomarkers of early progression in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy (RLT).
This 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.
A 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 < 6.0 were significantly and independently associated with early progression (respectively adjusted OR = 3.2; 95% CI: 1.02-10.6; p = 0.049 and adjusted OR = 12.6 ; 95% CI: 3.7-50.9; p < 0.001). PSMA-ligand SUVmean < 6.0 was also significantly and independently associated with a poorer overall survival (median overall survival = 11 months (95% CI: 5-24) vs. 22 months (95% CI: 15 - not reach) for patients with PSMA-ligand SUVmean ≥ 6.0; p = 0.019).
PSMA-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.
Annals of nuclear medicine. 2026 May 23 [Epub ahead of print]
Baptiste Mercier, Léane Dréano, Estelle Neveu, Florian Estrade, Romain Mathieu, Brigitte Laguerre, Laurence Crouzet, Antonin Broyelle, Christelle Bouvry, Florence Le Jeune, Julie Faudemer, Julien Farce, Xavier Palard-Novello
Department of Nuclear Medicine, CLCC Eugène Marquis, Avenue de la Bataille Flandres-Dunkerque, Rennes, 35000, France., Research Department, CLCC Eugène Marquis, Rennes, France., Department of Medical Oncology, CLCC Eugène Marquis, Rennes, France., Urology Department, Centre Hospitalier Universitaire de Rennes, Rennes, France., Department of Pharmacy, CLCC Eugène Marquis, Rennes, France., Univ Rennes, CLCC Eugène Marquis, INSERM, LTSI - UMR 1099, Rennes, France., Univ Rennes, CLCC Eugène Marquis, INSERM, LTSI - UMR 1099, Rennes, France. .