Artificial Intelligence-Based 18F-FDG PET/CT Radiomics for Mediastinal Lymph Node Staging in Non-Small Cell Lung Cancer: A Systematic Review

Background/Objectives: Accurate staging of mediastinal lymph nodes is essential for therapeutic decisions and prognostic assessment in non-small cell lung cancer (NSCLC). This systematic review evaluates diagnostic performance, validation strategies, and clinical significance of artificial intelligence (AI)-based 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET/CT) radiomics models for mediastinal nodal staging in NSCLC. Methods: Systematic literature searching was conducted in PubMed, ScienceDirect, and Scopus according to the PRISMA 2020 guidelines. Eligible studies used radiomic or AI-based approaches for mediastinal lymph node (LN) evaluation in NSCLC, with histopathology as a reference standard. Extracted data included study design, cohort characteristics, imaging method, validation strategy, and diagnostic performance metrics. Methodological quality was assessed by the QUADAS-2 tool. Results: Thirteen studies were included which are mainly retrospective in their designs with cohort sizes varying between 87 and 3265 patients. Models evaluated on external or prospective validation cohorts generally showed lower performance compared with training or internal datasets. However, clinically significant discriminative ability has been preserved across heterogeneous populations. In studies that directly compared methods, composite models integrating radiomic features with clinical factors and conventional PET metrics, sometimes including deep learning-derived features, consistently outperformed radiomics-only models. Additionally, selected approaches addressing FDG-related false-positive uptake improved distinction between benign and metastatic mediastinal lymph nodes; this is reflected by reduced false-positive classifications plus higher specificity compared with conventional PET/CT interpretation. Conclusions: AI-based 18F-FDG PET/CT radiomics show a promising discriminative capacity for mediastinal nodal staging in NSCLC, especially when it is integrated with clinical and conventional imaging variables. Although the model performance remains clinically significant within independent validation cohorts, attenuation compared with training datasets is commonly observed. Methodological heterogeneity, predominantly retrospective study designs, and the scarcity of prospective multicenter validation currently limit routine clinical implementation.