Real-world outcomes of 177LuLu-PSMA-I&T in 18FFDG-positive metastatic castration-resistant prostate cancer: factors related to response and survival

Abstract Background Little is known about predictors of response to radionuclide therapy with PSMA-ligands in patients with 18 FFDG-positive metastatic castration-resistant prostate cancer (mCRPC). We assessed the correlation between baseline characteristics, including dual tracer PET parameters, and response to 177 LuLu-PSMA-I&T in a cohort of patients with 18 FFDG-positive mCRPC. Prognostic factors related to progression-free survival (PFS) and overall survival (OS) were also investigated. Methods mCRPC patients who underwent 68 GaGa-PSMA-11 and 18 FFDG PET/CT prior to 177 LuLu-PSMA-I&T were retrospectively evaluated. Only 18 FFDG-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. Results Twenty-five 18 FFDG-positive patients who received 177 LuLu-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 68 GaGa-PSMA-11 SUV mean ( p = 0.022) and 68 GaGa-PSMA/ 18 FFDG SUV mean ratio ( p = 0.021) were significantly associated with PSA30 response. 68 GaGa-PSMA-11 SUV mean was also significant in the multivariate model. ROC analysis indicated an optimal 68 GaGa-PSMA-11 SUV mean cutoff value of 10.23 (AUC = 0.741), and a best discriminating 68 GaGa-PSMA/ 18 FFDG SUV mean cutoff ratio of 2.08 (AUC = 0.727). In the univariate analysis for radiological PFS (rPFS), high ALP ( p = 0.023), 68 GaGa-PSMA-11 MTV ( p = 0.011), 68 GaGa-PSMA-11 TLU ( p = 0.015), and 18 FFDG MTV ( p = 0.013) were significantly associated with shorter rPFS. 68 GaGa-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 68 GaGa-PSMA-11 MTV ( p = 0.003), 68 GaGa-PSMA-11 TLU ( p = 0.025), and 18 FFDG MTV ( p = 0.024). However, no independent predictors of OS were identified in the multivariate analysis. Conclusions Our preliminary results suggest that a whole-body 68 GaGa-PSMA-11 SUV mean higher than 10 and a 68 GaGa-PSMA-11/ 18 FFDG 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 18 FFDG-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.