18F-FDG PET/CT for detection of the primary tumor in adults with extracervical metastases from cancer of unknown primary: A systematic review and meta-analysis

Cancer of unknown primary (CUP) is a heterogeneous group of cancers, so called when a biopsy from a patient reveals malignancy without giving a clue to where in the body the primary tumor is located. Whole-body 18-fluorine-fluorodeoxyglucose positron-emission-tomography/computed tomography (18F-FDG PET/CT) is widely used for diagnosis and staging of most cancers. We hypothesized that 18F-FDG PET/CT-especially if used early-is suitable for the detection of the primary tumor in patients with CUP. To assess the ability of 18F-FDG PET/CT to detect the primary tumor in adult CUP patients. PubMed/Medline, Embase, and Web of Science. Studies on CUP from extracervical metastases in which every patient had received an 18F-FDG PET/CT scan and at least one 18F-FDG PET/CT-positive finding was confirmed by biopsy or clinical follow-up. PRISMA and QUADAS-2 were applied. The pooled detection rate (DR) of 18F-FDG PET/CT was assessed with a fixed-effects model. Heterogeneity among studies was assessed with the I-squared statistic. A total of 2953 articles were identified from which N = 82 were assessed by full text and N = 20, comprising 1942 adult patients, were included in the study. Median (range) number of patients and DR was N = 72 (21-316) and 36.3% (9.8%-75.3%), respectively. Two-thirds of included studies were retrospective, and the pooled DR was 40.93% (95% confidence interval: 38.99%-42.87%). There was large heterogeneity between studies (I-squared = 95.9%), randomization was not applied, CUP diagnosis was not standardized, and workup (if described) was characterized by multiple testing procedures resulting in a highly selected, challenging patient group. Despite great heterogeneity in diagnostic workup and in studies in general, an overall DR of 40.93% suggests that upfront application of 18F-FDG PET/CT may have a role in CUP by obviating a great many futile diagnostic procedures. To what degree 18F-FDG PET/CT used early in the course of disease may improve the detection rate could not be deducted from selected articles. A large, prospective, preferably randomized, study on the potential benefit of using 18F-FDG PET/CT up front in CUP patients is warranted to judge if and when 18F-FDG PET/CT should be applied in these patients.