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.

OBJECTIVE

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).

METHODS

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.

RESULTS

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).

CONCLUSIONS

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.