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 Ra-223 dichloride therapy (Ra-223) and to determine whether skeletal tumor burden on whole-body F-18-fluoride PET/CT can be used as a predictive biomarker.of survival in patients treated with Ra-223. Methods: Forty-two patients with hormone-refractory prostate cancer underwent Ra-223 and a baseline fluoride PET/CT scan. Fluoride PET/CT parameters were generated, including maximum standardized uptake value (SUVmax) of the hottest lesion (hSUV(max)), average SUV of disease (Mean(10)), 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 = 0.0212; hazard ratio = 5.990; 95% confidence interval = 1.306-27.475). A TLF10 cutoff value of 8,000 discriminated survivors from nonsurvivors after Ra-223 (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, Mean(10), and hSUV(max) were not predictors of OS or progression-free survival. Mean(10) 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 Meanio 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 Ra-223.