Prognostic factors in patients treated with 223Ra: The role of skeletal tumor burden on baseline ¹⁸F-fluoride PET/CT in predicting overall survival

The purpose of this study was to evaluate outcome after ²²³Ra dichloride therapy (²²³Ra) and to determine whether skeletal tumor burden on whole-body 18F-fluoride PET/CT can be used as a predictive biomarker of survival in patients treated with ²²³Ra. Methods: Forty-two patients with hormone-refractory prostate cancer underwent ²²³Ra and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUVmax), average SUV of disease (Mean₁₀), and skeletal tumor burden indices of total fluoride skeletal metastatic lesion uptake (TLF₁₀) and total volume of fluoride avid bone metastases (FTV10). Overall survival (OS) was the primary endpoint. Secondary endpoints were progression-free survival and skeletal-related event (SRE). Results: Skeletal tumor burden indices (TLF₁₀ and FTV₁₀) derived from fluoride PET/CT at baseline were highly correlated and significant independent predictors of OS (P 5 0.0212; hazard ratio 5 5.990; 95% confidence interval 5 1.306-27.475). A TLF10 cutoff value < 8,000 discriminated survivors from nonsurvivors after ²²³Ra (with TLF10 values < 8,000, the median OS was not estimated, whereas with TLF₁₀ < 8,000, the median OS was 6.67 mo). Visual analysis, Mean₁₀, and hSUVmax were not predictors of OS or progression-free survival. Mean₁₀ was found to be a significant univariate predictor of the odds of having an SRE (P = 0.0445; odds ratio = 1.30; 95% confidence interval = 1.006-1.681), with a Mean10 greater than 19 increasing the risk of SRE. Conclusion: Skeletal tumor burden on baseline fluoride PET/CT is a predictive biomarker of OS and the risk of an SRE in patients treated with ²²³Ra.