Prognostic Value of a Composite Score Incorporating Baseline [18F]FDG PET/CT and [68Ga]Ga-PSMA-11 PET/CT When Screening for [177Lu]Lu-PSMA Treatment Eligibility (PROFILE Study).

We investigated the prognostic value of baseline [18F]FDG and [68Ga]Ga-PSMA-11 PET/CT in patients with metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA-617. Methods: In this multicenter retrospective study, the associations between several clinical, biologic, and radiologic parameters and overall survival (OS) were tested in a development cohort using univariable analyses, followed by the construction of a multivariable Cox model. The PROFILE prognostic score was subsequently derived from this model, internally validated, and externally validated in an independent cohort. Results: Data from 174 patients from 3 centers were used to construct the multivariable Cox model. Five independent adverse prognostic factors were identified and incorporated into the PROFILE score: an SUVmax exceeding 300% of the PERCIST threshold on [18F]FDG PET/CT, a "nonhigh" classification on [68Ga]Ga-PSMA-11 PET/CT using the visual PSMA tumor-to-salivary gland ratio, a baseline hemoglobin level of 11 g/dL or less, a baseline alkaline phosphatase level of greater than 220 IU/L, and a disease duration not exceeding 100 mo. The PROFILE score stratified patients into 3 risk groups and achieved a Harrell C-index of 0.67 (95% CI, 0.62-0.72). The median OS in the low-, intermediate-, and high-risk groups was 17.2, 13.0, and 8.6 mo, respectively (P < 0.0001). These results were confirmed in 114 patients in an independent, single-center validation cohort, with median OS of 20.4, 14.3, and 8.8 mo (P < 0.0001), respectively, and a C-index of 0.73 (95% CI, 0.68-0.78). Conclusion: The PROFILE score offers valuable prognostic information for patients with metastatic castration-resistant prostate cancer when considering the use of [177Lu]Lu-PSMA-617 therapy.