Real-world outcomes of [¹⁷⁷Lu]Lu-PSMA-I&T in [¹⁸F]FDG-positive metastatic castration-resistant prostate cancer: factors related to response and survival.

Abstract

Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with [¹⁸F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to [¹⁷⁷Lu]Lu-PSMA-I&T in a cohort of patients with [¹⁸F]FDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated. mCRPC patients who underwent [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]FDG PET/CT prior to [¹⁷⁷Lu]Lu-PSMA-I&T were retrospectively evaluated. Only [¹⁸F]FDG-positive patients were included in the analysis. A semi-automatic segmentation tool was applied to measure the whole-body maximum standardized uptake value (SUV_max), mean standardized uptake value (SUV_mean), metabolic tumor volume (MTV), and total lesion uptake (TLU) on both PET/CTs. PSA response was defined as ≥ 30% and ≥ 50% decline. Imaging response, assessed two months after the last cycle, was defined according to RECIST 1.1 and/or PSMA PET progression (PPP) criteria. Clinical, biochemical, and imaging-based factors were correlated to response to treatment, PFS, and OS. Twenty-five [¹⁸F]FDG-positive patients who received [¹⁷⁷Lu]Lu-PSMA-I&T were included. PSA30 and PSA50 responses were achieved in 11/25 (44%) and in 9/25 (36%) patients, respectively. In the univariate analysis [⁶⁸Ga]Ga-PSMA-11 SUV_mean (p = 0.022) and [⁶⁸Ga]Ga-PSMA/[¹⁸F]FDG SUV_mean ratio (p = 0.021) were significantly associated with PSA30 response. [⁶⁸Ga]Ga-PSMA-11 SUV_mean was also significant in the multivariate model. ROC analysis indicated an optimal [⁶⁸Ga]Ga-PSMA-11 SUV_mean cutoff value of 10.23 (AUC = 0.741), and a best discriminating [⁶⁸Ga]Ga-PSMA/[¹⁸F]FDG SUV_mean cutoff ratio of 2.08 (AUC = 0.727). In the univariate analysis for radiological PFS (rPFS), high ALP (p = 0.023), [⁶⁸Ga]Ga-PSMA-11 MTV (p = 0.011), [⁶⁸Ga]Ga-PSMA-11 TLU (p = 0.015), and [¹⁸F]FDG MTV (p = 0.013) were significantly associated with shorter rPFS. [⁶⁸Ga]Ga-PSMA-11 MTV showed a borderline association with rPFS in the multivariate model (p = 0.061). Hemoglobin levels (p = 0.008), ALP (p = 0.018) and PSA (p = 0.023) values before treatment were associated with OS, as well as [⁶⁸Ga]Ga-PSMA-11 MTV (p = 0.003), [⁶⁸Ga]Ga-PSMA-11 TLU (p = 0.025), and [¹⁸F]FDG MTV (p = 0.024). However, no independent predictors of OS were identified in the multivariate analysis. Our preliminary results suggest that a whole-body [⁶⁸Ga]Ga-PSMA-11 SUV_mean higher than 10 and a [⁶⁸Ga]Ga-PSMA-11/[¹⁸F]FDG SUV_mean ratio > 2 may serve as useful predictors for identifying patients likely to achieve at least a 30% reduction in PSA levels, even among [¹⁸F]FDG-positive mCRPC patients. Furthermore, our findings support the prognostic significance of tumor burden either calculated by imaging-based volumetric parameters or by known biochemical markers of disease.