Role of FAPI PET/CT in cancer of unknown primary (CUP): A systematic review

This systematic review analyzes the value of FAPI PET/CT in diagnosing cancer of unknown primary (CUP). CUP is a metastatic malignant disease in which the site of origin cannot be determined. It accounts for 3-5 % of all malignant neoplasms and has a poor prognosis with a median survival of 6 to 9 months. Currently, CT, MRI and [¹⁸F]FDG PET/CT are the preferred imaging modalities. FAPI PET/CT has been shown to outperform [¹⁸F]FDG in a wide range of oncological settings and this promising radioligand could benefit the management of CUP by improving the detection rate of the primary site. A systematic search revealed four studies that met our inclusion criteria. Two studies focused on CUP in the head and neck region and two on general CUP. In the head and neck group FAPI PET/CT has a significantly higher tumor-to-background ratio (TBR) and a better detection rate of the primary site compared to [¹⁸F]FDG PET/CT. Also in the general group, FAPI PET showed a higher SUV_max and TBR in CUP patients compared to [¹⁸F]FDG PET and one study reported identification of the primary site in 68% (30/44). These results suggest that FAPI PET/CT provides superior sensitivity in detecting both primary tumors and metastatic lesions, particularly in cases in which [¹⁸F]FDG PET/CT is less effective. This highlights the potential of FAPI PET/CT to enhance diagnostic accuracy in oncology, especially for patients with challenging cases.