68Ga-FAPI PET/CT in diagnosis, staging and management of gastric carcinoma: A systematic review and meta-analysis.

OBJECTIVES: Gastric carcinoma is a major cause of cancer related mortality worldwide. Accurate staging, including detection of nodal and distant metastases, is essential for treatment planning. Conventional 18F-FDG PET/CT has important limitations in gastric cancer, especially in diffuse and mucinous histologic subtypes. Fibroblast activation protein inhibitor (FAPI) PET/CT targets cancer-associated fibroblasts and may improve lesion conspicuity.To systematically review and meta-analyse the diagnostic performance of 68Ga-FAPI PET/CT for staging of gastric carcinoma and, in studies with head-to-head data, to compare it with 18F-FDG PET/CT. METHODS: This review followed PRISMA 2020 recommendations. The protocol was prospectively registered in PROSPERO (CRD420251056976). PubMed, EMBASE, Web of Science and Cochrane libraries were searched from January 2016 to December 2023 for clinical studies evaluating 68Ga-FAPI PET/CT in histologically confirmed gastric carcinoma. Two reviewers independently screened records, extracted data, and assessed risk of bias using QUADAS-2. For 68Ga-FAPI PET/CT, per patient 2×2 tables were constructed for detection of primary tumors and metastatic sites. Pooled sensitivity, specificity, positive and negative predictive values and accuracy were estimated using random effects models. Summary ROC (SROC) and hierarchical SROC (HSROC) curves were generated. Comparative analyses with 18F-FDG PET/CT were restricted to studies with head to head data in the same patient cohort, and areas under the curve (AUCs) were compared with DeLong's test. RESULTS: Fourteen studies (661 patients) were included; nine provided head to head comparisons with 18F-FDG PET/CT. For detection of primary gastric carcinoma with 68Ga-FAPI PET/CT, pooled sensitivity and specificity were 95-96% and 93% respectively, with an AUC of 0.96 (95% CI ~ 0.89-1.00). For metastatic disease, pooled accuracy for lymph node, omental, visceral and skeletal metastases ranged from ~89% to 97%. In head to head studies, 68Ga-FAPI PET/CT showed higher AUCs than 18F-FDG PET/CT for primary tumors (0.96 vs 0.76; p=0.001) and omental metastases (0.97 vs 0.78; p=2.6×10⁻⁵). Heterogeneity was moderate for most outcomes. Funnel plots and trim and fill analyses suggested possible small study effects, but adjusted pooled diagnostic odds ratios remained high. CONCLUSIONS: 68Ga-FAPI PET/CT demonstrates high diagnostic accuracy for staging of gastric carcinoma and appears to outperform 18F-FDG PET/CT in many settings, particularly for omental and some visceral metastases and for histologic subtypes with low FDG avidity. These findings support the use of 68Ga-FAPI PET/CT as a promising complementary imaging modality for staging and restaging, but not as a stand-alone diagnostic test. Larger, prospective multicentre studies with standardized protocols are required before routine guideline incorporation.