18FFDG PET/CT versus Bone Scintigraphy for the Diagnosis of Bone Metastasis in Breast Cancer: A Systematic Review and Meta-Analysis

Breast cancer has become the most commonly diagnosed cancer in women worldwide, with advanced cases often leading to bone metastases that significantly affect prognosis and quality of life. This meta-analysis and systematic review aims to evaluate and compare the diagnostic performance of 18FFDG PET/CT and bone scintigraphy for detecting bone metastases in breast cancer patients. A systematic search was conducted across PubMed, Embase, Web of Science, and Scopus for studies published up to February 2025. Relevant articles were identified using a combination of subject-specific and free-text keywords, including "breast cancer," "positron emission tomography," "bone scintigraphy," and "bone metastasis." Studies assessing the diagnostic utility of 18FFDG PET/CT and bone scintigraphy in detecting bone metastases were included. A bivariate random-effects model was used to calculate pooled estimates of sensitivity, specificity, and diagnostic accuracy with 95% confidence intervals (CIs). Potential sources of heterogeneity were explored using meta- regression analysis. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS- 2) tool was applied to evaluate the methodological quality of the included studies. A total of 1407 publications were initially retrieved, and 13 studies involving 892 patients met the inclusion criteria. The pooled diagnostic performance for 18FFDG PET/CT demonstrated a sensitivity of 0.91 (95% CI: 0.81-0.96) and a specificity of 0.98 (95% CI: 0.93-1.00), with an area under the curve (AUC) of 0.99 (95% CI: 0.97-0.99). In comparison, bone scintigraphy showed a sensitivity of 0.82 (95% CI: 0.72-0.89), specificity of 0.81 (95% CI: 0.73-0.87), and an AUC of 0.88 (95% CI: 0.85-0.91). Despite its higher diagnostic accuracy, PET/CT exhibited notable heterogeneity across studies, potentially influenced by differences in patient populations and imaging interpretation criteria. Our meta-analysis demonstrated the superior diagnostic performance of 18FFDG PET/CT over bone scintigraphy, likely attributable to its enhanced sensitivity for osteolytic lesions and integrated anatomical-functional imaging. Nevertheless, considerable inter-study heterogeneity and incomplete clinical data reporting limit the generalizability and robustness, warranting further standardized prospective investigations. The findings suggest that 18FFDG PET/CT offers superior diagnostic accuracy compared to bone scintigraphy for detecting bone metastases in breast cancer patients. However, its clinical application requires further validation through large-scale, prospective studies. Additionally, considerations such as cost-effectiveness and accessibility must be addressed before widespread clinical adoption.