Imaging and Clinical Correlates of [177Lu]Lu-PSMA PET-Defined Eligibility in De Novo Metastatic Prostate Cancer

Objectives: Eligibility for Lutetium-177 labeled prostate-specific membrane antigen ([177Lu]Lu-PSMA) radioligand therapy depends on PSMA PET/CT interpretation and may vary across observers and centres. We aimed to identify imaging and clinical correlates of VISION-like PSMA PET-defined eligibility and to compare exploratory clinical, PET-based, and combined models. Materials and Methods: Seventy-six consecutive patients with de novo metastatic prostate cancer undergoing PSMA PET/CT were retrospectively assessed for [177Lu]Lu-PSMA eligibility. Candidacy was determined by consensus of two nuclear medicine physicians using VISION-like criteria. Three stepwise logistic regression models used clinical variables, PSMA PET/CT variables, or both, and were internally validated with bootstrap out-of-bag predictions. Results: Forty-three patients (56.6%) met VISION-like criteria for RLT. Internally validated area under the curve (AUC) values were 0.731, 0.817, and 0.829 for the clinical, PSMA PET/CT, and combined models. PET-defined candidacy was associated with higher PSMA-positive lesion count, greater PET-derived tumour burden, and higher mean standardised uptake value (SUVmean). Clinically, CHAARTED low-volume disease and prior docetaxel exposure were linked to lower probability, whereas disease state at imaging was not significant. In the combined multivariable model, SUVmean was independently associated with higher candidacy (odds ratio [OR]: 1.22, 95% confidence interval [CI]: 1.04–1.42; p = 0.015), whereas prior docetaxel showed the opposite association (OR: 0.10, 95% CI: 0.0129–0.776; p = 0.028). Conclusions: PSMA-positive lesion count and SUVmean were the most reproducible determinants of VISION-like eligibility. Prior docetaxel exposure was associated with lower candidacy in the combined model, although the exposed subgroup was small and the confidence interval wide. Whether systemic therapy modifies PSMA expression, and with it access to subsequent PSMA-targeted lines, requires paired imaging before and after treatment in the same patients.