Head-To-Head Comparison of 68Ga-FAPI PET/CT and FDG PET/CT for the Detection of Peritoneal Metastases: Systematic Review and Meta-Analysis

BACKGROUND. FDG PET/CT has limited diagnostic performance in the detection of peritoneal metastasis (PM). Gallium-68-labeled fibroblast activation protein inhibitor (FAPI) targets tumor stroma, leading to high accumulation across cancer types. OBJECTIVE. The purpose of this study was to conduct a meta-analysis to compare the diagnostic performances of Ga-68-FAPI PET/CT and FDG PET/CT in detecting PM on the basis of studies providing head-to-head comparisons between the two tests. EVIDENCE ACQUISITION. PubMed, Embase, and Cochrane Library databases were searched through July 2022 to identify studies reporting head-to-head comparison of Ga-68-FAPI PET/CT and FDG PET/CT for detection of PM. The reference standard was classified as histopathology for all patients or as a combination of histopathologic, clinical, imaging, laboratory, and follow-up information (multidisciplinary reference standard). A random-effects statistical model was applied to conduct a meta-analysis of the diagnostic performances of the tests in patient-based and lesion-based analyses. The QUADAS-2 and QUADAS Comparative tools were used to assess study quality. EVIDENCE SYNTHESIS. Eleven studies were included. Patient-based analysis was reported in nine studies including 340 patients, and lesion-based analysis was reported in four studies including 222 lesions. The pooled sensitivity of Ga-68-FAPI PET/CT was significantly higher than that of FDG PET/CT in patient-based analysis (98.2% [95% CI, 96.1-100.0%] vs 55.9% [95% CI, 33.9-77.9%]) and lesion-based analysis (99.9% [95% CI, 99.5-100.0%] vs 27.3% [95% CI, 11.2-43.4%]). Eight studies were rated at high risk of bias in the reference standard domain because the multidisciplinary reference standard was not sufficiently explained and may have included one of the two index tests, which would have artificially increased sensitivity. In three studies specificity was reported as 100.0% for both tests; these studies were considered at uncertain risk of bias in the patient selection domain because patients with benign peritoneal conditions may have been excluded, resulting in underestimation of potential false-positive results. CONCLUSION. The current evidence suggests excellent sensitivity of Ga-68-FAPI PET/ CT for the detection of PM in comparison with poorer sensitivity of FDG PET/CT. However, most included studies had high risk of bias. Further studies are needed to more convincingly characterize true- and false-positive results. CLINICAL IMPACT. The sensitivity of Ga-68-FAPI PET/CT may be substantially greater than that of FDG PET/CT for the evaluation of PM, facilitating surgical planning and candidate selection.