Real-world outcomes of [177Lu]Lu-PSMA-I&T in [18F]FDG-positive metastatic castration-resistant prostate cancer: factors related to response and survival.
Higher [68Ga]Ga-PSMA-11 SUVmean and SUVmean ratio may predict PSA response in [18F]FDG-positive mCRPC patients, but further research is needed.
Where it sits
this study against the rest of the vipivotide corpusSummary and findings
The study evaluated the correlation between baseline characteristics and response to [177Lu]Lu-PSMA-I&T in 25 [18F]FDG-positive metastatic castration-resistant prostate cancer patients. PSA30 and PSA50 responses were achieved in 44% and 36% of patients, respectively. [68Ga]Ga-PSMA-11 SUVmean and SUVmean ratio were significant predictors of PSA30 response.
Abstract
Background 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. Methods 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 (SUVmax), mean standardized uptake value (SUVmean), 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 [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 SUVmean (p = 0.022) and [68Ga]Ga-PSMA/[18F]FDG SUVmean ratio (p = 0.021) were significantly associated with PSA30 response. [68Ga]Ga-PSMA-11 SUVmean was also significant in the multivariate model. ROC analysis indicated an optimal [68Ga]Ga-PSMA-11 SUVmean cutoff value of 10.23 (AUC = 0.741), and a best discriminating [68Ga]Ga-PSMA/[18F]FDG SUVmean 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. Conclusions Our preliminary results suggest that a whole-body [68Ga]Ga-PSMA-11 SUVmean higher than 10 and a [68Ga]Ga-PSMA-11/[18F]FDG SUVmean 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.
Background
The study addresses the need for understanding predictors of response to radionuclide therapy with PSMA-ligands in [18F]FDG-positive metastatic castration-resistant prostate cancer (mCRPC). Prior knowledge on this topic is limited, making it crucial to identify factors that correlate with treatment response and survival outcomes. This research is significant as it explores potential imaging and biochemical markers that could guide therapeutic decisions.
Methods
This was a retrospective study involving 25 mCRPC patients who were [18F]FDG-positive. Patients underwent [68Ga]Ga-PSMA-11 and [18F]FDG PET/CT prior to receiving [177Lu]Lu-PSMA-I&T therapy. The study utilized a semi-automatic segmentation tool to measure SUVmax, SUVmean, metabolic tumor volume (MTV), and total lesion uptake (TLU) on PET/CT scans. PSA response was defined as a decline of ≥30% and ≥50%, with imaging response assessed two months post-treatment using RECIST 1.1 and/or PSMA PET progression criteria.
Results
In this cohort, 44% of patients achieved a PSA30 response, and 36% achieved a PSA50 response. The [68Ga]Ga-PSMA-11 SUVmean and the [68Ga]Ga-PSMA/[18F]FDG SUVmean ratio were significantly associated with PSA30 response, with p-values of 0.022 and 0.021, respectively. An optimal [68Ga]Ga-PSMA-11 SUVmean cutoff value of 10.23 was identified, with an AUC of 0.741. High ALP, [68Ga]Ga-PSMA-11 MTV, and TLU were associated with shorter radiological progression-free survival (rPFS). Hemoglobin, ALP, and PSA levels before treatment, along with [68Ga]Ga-PSMA-11 MTV and TLU, were associated with overall survival (OS), though no independent predictors of OS were found in multivariate analysis.
Interpretation
The findings suggest that specific imaging parameters, such as [68Ga]Ga-PSMA-11 SUVmean, can predict PSA response in [18F]FDG-positive mCRPC patients. While these predictors are statistically significant, the clinical significance remains to be fully established due to the small sample size and retrospective nature of the study. The study contributes to the understanding of prognostic factors in mCRPC but requires validation in larger, prospective trials to confirm these preliminary results.
Key findings
- PSA30 response in 44% of patients.
- PSA50 response in 36% of patients.
- [68Ga]Ga-PSMA-11 SUVmean p=0.022 for PSA30 response.
- [68Ga]Ga-PSMA/[18F]FDG SUVmean ratio p=0.021 for PSA30 response.
- Optimal [68Ga]Ga-PSMA-11 SUVmean cutoff value of 10.23, AUC=0.741.
Limitations
- Small n=25
- Retrospective design
- Single-center study
- No independent predictors of OS in multivariate analysis