Positron Emission Tomography/Computed Tomography in Bladder Cancer: The Role of 18FFDG and Non-FDG Radiotracers

Background and Objectives: Bladder cancer is one of the most common malignancies of the urinary tract and poses a significant clinical challenge due to its biological heterogeneity and high rates of recurrence and progression. Urothelial carcinoma represents the predominant histological subtype, ranging from non-muscle-invasive disease with relatively favorable outcomes to aggressive muscle-invasive and metastatic forms associated with poor prognosis. Accurate diagnosis, staging, prognostic stratification, and assessment of treatment response are therefore essential for optimal patient management. The objective of this review is to summarize and critically evaluate the current evidence on the role of positron emission tomography/computed tomography (PET/CT) in bladder cancer, with particular emphasis on 18FFDG PET/CT and non-FDG radiotracers. Materials and Methods: A narrative review of the available literature was performed, focusing on clinical studies, review articles, and guideline documents addressing the use of PET/CT in bladder cancer. The literature search included articles published between 2000 and 2025, while earlier landmark studies were selectively included if considered historically important for understanding the development of PET/CT imaging in bladder cancer. The initial search yielded over 500 records; after screening titles and abstracts, more than 100 articles were selected for full-text evaluation. The analyzed evidence encompasses the clinical applications of 18FFDG PET/CT and alternative radiotracers, including choline-, acetate-, methionine-, and sodium fluoride-based tracers, and fibroblast activation protein inhibitors (FAPI), across different stages of disease and clinical settings. Results: Conventional imaging modalities, such as computed tomography and magnetic resonance imaging, provide important anatomical information but remain limited in the evaluation of lymph node involvement, early metastatic disease, treatment response, and disease recurrence. Despite limitations related to physiological urinary excretion, 18FFDG PET/CT has demonstrated clinical value in selected scenarios, particularly for staging, prognostic assessment, detection of recurrence, and response evaluation. To overcome FDG-related constraints, several non-FDG radiotracers have been investigated. Among these, FAPI PET/CT has emerged as a promising modality due to its ability to target the tumor stroma, potentially improving lesion detectability and tumor-to-background contrast. Conclusions: This review summarizes and critically evaluates current evidence on the role of PET/CT in bladder cancer, with a focus on 18FFDG PET/CT and non-FDG radiotracers. The discussed studies highlight their applications in primary diagnosis, staging, prognostic assessment, detection of recurrence, and evaluation of treatment response, as well as their respective advantages and limitations. Furthermore, potential future directions for PET/CT imaging in clinical practice are outlined, emphasizing the need for further research to clarify the optimal use of established and emerging radiotracers.