Prognostic Value of [¹⁸F]FDG PET Combined with [⁶⁸Ga]Ga-PSMA PET as Pretreatment Imaging in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with [¹⁷⁷Lu]Lu-PSMA-617.

Abstract

Prostate-specific membrane antigen (PSMA)-targeted radiopharmaceutical therapy with [¹⁷⁷Lu]Lu-PSMA-617 has reshaped the management of metastatic castration-resistant prostate cancer (mCRPC). This study aimed to assess the added prognostic value of [¹⁸F]FDG PET beyond [⁶⁸Ga]Ga-PSMA-11 PET as pretreatment imaging and to develop an overall survival (OS) nomogram for patients with mCRPC who were treated with [¹⁷⁷Lu]Lu-PSMA-617. <b>Methods:</b> From February 2022 to November 2023, all patients with mCRPC treated with at least 1 cycle of [¹⁷⁷Lu]Lu-PSMA-617 were analyzed. Baseline [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]FDG PET parameters (SUV_max, SUV_mean, total metabolic tumor volume [TMTV], and total lesion activity) were extracted for both tracers. OS was modeled using 2 hierarchical least absolute shrinkage and selection operator Cox models: clinical covariates plus [⁶⁸Ga]Ga-PSMA-11 PET (M-PSMA) and clinical covariates plus [⁶⁸Ga]Ga-PSMA-11 PET plus [¹⁸F]FDG PET (M-PSMA + FDG). Model discrimination was assessed using the optimism-corrected Harrell concordance index (C-index), whereas model improvement was assessed with changes in the C-index. <b>Results:</b> The study included 99 patients with mCRPC, and the median OS was 14 mo (95% CI, 11.7-18.2 mo). In M-PSMA, the [⁶⁸Ga]Ga-PSMA-11 PET SUV_mean was the only significant imaging parameter (hazard ratio, 0.897; 95% CI, 0.852-0.945; <i>P</i> < 0.001). The addition of TMTV [¹⁸F]FDG PET in M-PSMA + FDG yielded a modest improvement in prognostic performance (ΔC-index, 0.010; 95% CI, -0.021 to 0.044) but a refined risk prediction for patients with a high TMTV [¹⁸F]FDG burden. The final model was used to construct a nomogram for predicting 12-mo OS probability. <b>Conclusion:</b> Quantitative [⁶⁸Ga]Ga-PSMA-11 PET parameters provide strong prognostic stratification in patients with mCRPC who were treated with [¹⁷⁷Lu]Lu-PSMA-617. Tumor burden, as measured on [¹⁸F]FDG PET, adds incremental prognostic information beyond [⁶⁸Ga]Ga-PSMA-11 PET, resulting in a modest improvement in risk prediction and potential refinement of prognosis in selected high-risk patients.