Lung cancer is recognized as the most typical diagnosis malignancy globally, also notable for its high mortality rates (1). Lung cancer remains the most prevalent cancer globally in 2022, accounting for approximately 2.5 million new cases, which represents one in eight cancer diagnoses worldwide (12.4% of all global cancer incidences) (2). In this setting, roughly 80% of lung malignancies are categorized as non-small cell lung cancer (NSCLC), which is the main cancer diagnosis worldwide (3, 4). Surgery, radiation, chemotherapy, immunotherapy, and targeted therapy can all be used to treat NSCLC, depending on the stage of the tumor (5). The effectiveness of these treatments and the overall prognosis of the patient are profoundly impacted by the initial stage of the cancer (6). As a result, thorough and precise imaging-based staging is important for optimal care of NSCLC patients.

Currently, clinical methods used for NSCLC staging include computed tomography (CT), magnetic resonance imaging (MRI), and biopsy (7, 8). However, each of these modalities has its inherent limitations. While CT scanning excels in identifying the tumor’s location and determining lymph node enlargement, its limited ability to determine or exclude mediastinal metastasis imposes certain constraints on the accurate staging of lung cancer (9). MRI is often considered less effective than CT for detecting small cancer lesions, due to its sensitivity to cardiac and respiratory motion artifacts, extremely low T2 values, lung magnetic field heterogeneity, and the low proton density of lung parenchyma (10). Biopsies, although crucial for delivering definitive results, are associated with inherent risks and may not always be feasible. The most common complication encountered is pneumothorax, which occurs in 20–64% of all CT-guided biopsies (11, 12). Additionally, hemorrhage from the lung parenchyma stands as another notable complication, frequently resulting from the needle track crossing a pulmonary vessel (13).

Positron emission tomography (PET) plays a crucial role in diagnosing NSCLC, from initial detection to staging and monitoring tumor metastasis (14). Integrating PET with 18F-fluorodeoxyglucose ([¹⁸F]FDG) into PET/CT and PET/MRI systems has considerably revolutionized cancer imaging by integrating metabolic and anatomical information (15). [¹⁸F]FDG PET/CT plays an important role in managing NSCLC, notably in evaluating the nodal status and finding occult metastatic disease, where it outperforms the capabilities of CT scanning alone (16). The NCCN guidelines emphasize the importance of rapid access to PET/CT for accurate staging in NSCLC, highlighting its role in guiding management decisions and predicting prognosis across all stages of the disease, particularly in detecting metastases (17). One of its main benefits over traditional imaging approaches is its increased sensitivity for detecting extra-thoracic metastases (18, 19). Dahlsgaard-Wallenius et al. found that PET/MRI and PET/CT had comparable diagnostic capacities for N-staging in NSCLC (20). Combining the metabolic data from PET with the special characteristics of MRI—such as low radiation exposure and excellent soft tissue contrast—makes PET/MRI an advantageous test (21). In several studies, evidence suggested that PET/MRI may outperform PET/CT in detecting metastases within the pleura, brain, liver, and bone (22, 23). This is also in accordance with the results of a prospective single-center research of 330 exams, where PET/MRI found brain and liver metastases that were undetectable by PET/CT (24). Thus, the use of a hybrid PET/MRI in lung cancer patients may sometimes assist the detection of distant metastases, because NSCLC metastases are primarily situated in the brain, liver, and bone (25, 26). However, the included trials gave minimal data on extra-thoracic metastatic illness, making it unable to draw conclusions about the potential advantage of PET/MRI. Due to the relative novelty of PET/MRI and the limited availability of direct comparison studies, inconsistencies in the literature regarding their comparative efficacy warrant careful examination.

The goal of this meta-analysis is to comprehensively evaluate the diagnostic performance of [¹⁸F]FDG PET/MRI to [¹⁸F]FDG PET/CT in NSCLC through head-to-head comparison.

The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy (PRISMA-DTA) standards (27). The protocol for this meta-analysis is registered with PROSPERO (CRD42023479817).

The continuing controversy in the field of nuclear medicine regarding the comparative usefulness of [¹⁸F]FDG PET/CT and [¹⁸F]FDG PET/MRI in the assessment of lymph node and distant metastases in NSCLC requires a comprehensive meta-analysis (20, 22, 23). This analysis is critical for elucidating the diagnostic accuracy of these modalities, thereby informing clinical decision-making.

Our meta-analysis incorporated six studies to compare these imaging techniques. We discovered that [¹⁸F]FDG PET/CT had a pooled sensitivity of 0.82 and specificity of 0.88 in identifying lymph node metastases, whereas [¹⁸F]FDG PET/MRI had a sensitivity of 0.86 and specificity of 0.90, with no significant differences identified. Similarly, in identifying distant metastases, [¹⁸F]FDG PET/CT had a sensitivity of 0.86 and specificity of 0.89, whereas [¹⁸F]FDG PET/MRI had a sensitivity of 0.93 and specificity of 0.90, with no significant differences found. The slightly higher sensitivity of PET/MRI may be attributed to its superior soft tissue contrast provided by MRI, which enables better differentiation between tissues, especially in complex anatomical areas such as the lungs and lymph nodes (35). Unlike PET/CT, which uses X-ray imaging, MRI offers much higher resolution for soft tissue, allowing for more accurate detection of small or ambiguous lesions (36). However, the overlapping confidence intervals suggest that these differences might not be clinically significant.

Compared to the previous studies by Mojahed et al. (37) and Zhang et al. (35), which evaluated the diagnostic accuracy of [¹⁸F]FDG PET/CT versus [¹⁸F]FDG PET/MRI in T and N staging, our analysis reveals equivalent effectiveness of these modalities in detecting N and M stages in NSCLC patients. However, unlike Mojahed et al. and Zhang et al., we included evaluations of distant metastases, a crucial aspect of NSCLC staging. In addition to building on the previous analyses, our meta-analysis incorporates four new studies (23, 31, 32, 34), particularly those focusing on M stage (distant metastasis) assessment (23, 31, 32). This addition provides a more comprehensive understanding of [18F]FDG PET/MRI’s capabilities, addressing both nodal and metastatic assessments in NSCLC staging.

Zhang et al.’s (21) meta-analysis included 14 papers, five of which focused on lung cancer. In an analysis of five lung cancer trials including 429 patients, [¹⁸F]FDG PET/CT exhibited better sensitivity (0.87 vs. 0.84) and slightly worse specificity (0.95 vs. 0.96) than PET/MRI. In contrast, our meta-analysis found that [¹⁸F]FDG PET/MRI had similar sensitivity and specificity to [¹⁸F]FDG PET/CT in detecting lymph nodes and distant metastases in NSCLC patients. The discrepancy may stem from several factors. One key reason could be that Zhang et al.’s meta-analysis included patients with small cell lung cancer in addition to those with NSCLC. Small cell lung cancer generally presents with different patterns of lymph node and metastatic involvement compared to NSCLC, which may affect the diagnostic performance of [¹⁸F]FDG PET/CT and PET/MRI.

While PET/CT and PET/MRI modalities offer similar diagnostic efficacy, their cost and accessibility differ markedly, influencing their clinical integration. PET/CT, significantly more affordable, emerges as a cost-effective solution for healthcare providers (38). Its broader availability enhances its utility across diverse medical environments, proving especially advantageous in areas lacking advanced medical infrastructure. In instances where both techniques yield comparable sensitivity and specificity, PET/CT is frequently the preferred option. This preference stems not only from its cost-efficiency and wider accessibility, which promote extensive use, but also from its role in fostering more equitable healthcare access, particularly in under-resourced regions. Thus, balancing sophisticated diagnostic capabilities for practicalities such as affordability and accessibility, PET/CT distinctly outperforms when both modalities present equivalent diagnostic outcomes (36). A comprehensive comparison of the pros and cons of both imaging modalities is detailed in Supplementary Table S2.

Our study has some limitations. The inclusion of only six studies, and our analysis limited by the lack of detailed diagnostic performance data for different organ sites of metastasis, suggests a need for more extensive research in this area. Additionally, not all patients underwent pathological biopsy, some diagnoses were based on a combination of biopsy and clinical imaging follow-up. Future research should focus on studies using pathology as the sole gold standard to further validate these findings.

Our meta-analysis shows that [¹⁸F]FDG PET/MRI has similar sensitivity and specificity to [¹⁸F]FDG PET/CT in identifying lymph node and distant metastases in patients with NSCLC. Additional larger sample prospective studies are needed to confirm these findings.