Detection of distant interval metastases after neoadjuvant therapy for esophageal cancer with 18F-FDG PET(/CT) : a systematic review and meta-analysis

Restaging after neoadjuvant therapy aims to reduce the number of patients undergoing esophagectomy in case of distant (interval) metastases. The aim of this study is to systematically review and meta-analyze the diagnostic performance of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) and 18F-FDG PET/CT for the detection of distant interval metastases after neoadjuvant therapy in patients with esophageal cancer. PubMed/MEDLINE, Embase, and the Cochrane library were systematically searched. The analysis included diagnostic studies reporting on the detection of distant interval metastases with 18F-FDG PET(/CT) in patients with esophageal cancer who received neoadjuvant therapy and both baseline staging and restaging after neoadjuvant therapy with 18F-FDG PET(/CT) imaging. The primary outcome measure was the proportion of patients in whom distant interval metastases were detected by 18F-FDG PET(/CT) as confirmed by pathology or clinical follow-up (i.e. true positives). The secondary outcome measure was the proportion of patients in whom 18F-FDG PET(/CT) restaging was false positive for distant interval metastases (i.e. false positives). Risk of bias and applicability concerns were assessed using the QUADAS-2 tool. Random-effect models were used to estimate pooled outcomes and examine potential sources of heterogeneity. Fourteen studies were included comprising a total of 1,110 patients who received baseline staging with 18F-FDG PET(/CT) imaging of whom 1,001 (90%) underwent restaging with 18F-FDG PET(/CT) imaging. Studies were generally of moderate quality. The pooled proportion of patients in whom true distant interval metastases were detected by 18F-FDG PET(/CT) restaging was 8% (95% confidence interval [CI]: 5-13%). The pooled proportion of patients in whom false positive distant findings were detected by 18F-FDG PET(/CT) restaging was 5% (95% CI: 3-9%). In conclusion,18F-FDG PET(/CT) restaging after neoadjuvant therapy for esophageal cancer detects true distant interval metastases in 8% of patients. Therefore, 18F-FDG PET(/CT) restaging can considerably impact on treatment decision-making. However, false positive distant findings occur in 5% of patients at restaging with 18F-FDG PET(/CT), underlining the need for pathological confirmation of suspected lesions