Background: Mediastinal staging plays a critical role in guiding treatment decisions for non-small cell lung cancer (NSCLC). While mediastinoscopy has been the gold standard for assessing mediastinal lymph node involvement, endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has emerged as a minimally invasive alternative with comparable diagnostic accuracy. This systematic review evaluates the diagnostic performance, safety, cost-effectiveness, and feasibility of EBUS-TBNA versus mediastinoscopy for mediastinal staging. Methods: A systematic literature review was conducted in accordance with PRISMA guidelines, including searches in Medline, Scopus, EMBASE, and Cochrane databases for studies published from 2010 onwards. A total of 1542 studies were identified, and after removing duplicates and applying eligibility criteria, 100 studies were included for detailed analysis. The extracted data focused on sensitivity, specificity, complications, economic impact, and patient outcomes. Results: EBUS-TBNA demonstrated high sensitivity (85–94%) and specificity (~100%), making it an effective first-line modality for NSCLC staging. Mediastinoscopy remained highly specific (~100%) but exhibited slightly lower sensitivity (86–90%). EBUS-TBNA had a lower complication rate (~2%) and was more cost-effective, while mediastinoscopy provided larger biopsy samples, essential for molecular and histological analyses. The need for general anaesthesia, longer hospital stays, and increased procedural costs make mediastinoscopy less favourable as an initial approach. Combining both techniques in select cases enhanced overall staging accuracy, reducing false negatives and improving diagnostic confidence. Conclusions: EBUS-TBNA has become the preferred first-line mediastinal staging method due to its minimally invasive approach, high diagnostic accuracy, and lower cost. However, mediastinoscopy remains crucial in cases requiring posterior mediastinal node assessment or larger tissue samples. The integration of both techniques in a stepwise diagnostic strategy offers the highest accuracy while minimizing risks and costs. Given the lower hospitalization rates and economic benefits associated with EBUS-TBNA, its widespread adoption may contribute to more efficient resource utilization in healthcare systems.

Purpose: To evaluate whether proton MR spectroscopy (¹H-MRS) improves the differentiation of tumoral from non-tumoral intracranial lesions beyond conventional MRI, and to quantify its effect on diagnostic confidence, in a consecutive real-world bicentric cohort of diagnostically ambiguous lesions. Methods: This retrospective, bicentric observational study screened 122 consecutive patients who underwent brain MRI with ¹H-MRS at two imaging centers, of whom 99 were eligible for final analysis after excluding 23 patients due to insufficient follow-up (<12 months) or incomplete reference standard. The reference standard was histopathological confirmation in 43 cases (43.4%) and structured clinico-radiological follow-up of at least 12 months in 56 cases (56.6%). The reporting radiologist’s binary diagnostic impression and confidence score were recorded before and after ¹H-MRS. Conventional MRI alone was compared to MRI plus ¹H-MRS using the exact McNemar test; Cho/NAA discrimination was assessed by ROC analysis with bootstrap confidence intervals, and confidence change by the Wilcoxon signed-rank test. Secondary analyses comprised an intention-to-diagnose analysis of all 99 examinations, counting non-diagnostic spectra as test failures, and an evaluable-case sensitivity analysis restricted to histopathologically confirmed patients with interpretable spectra. Results: Of 99 examinations, 89 (89.9%) yielded interpretable spectra. In the primary analysis, qualitative MRS interpretation demonstrated sensitivity of 76.0% (95% CI: 61.8–86.9), specificity of 94.9% (95% CI: 82.7–99.4), and accuracy of 84.3% (CI: 75.0–91.1), compared with 54.0%, 89.7% and 69.7% (59.0–79.0) for conventional MRI alone (exact McNemar p = 0.024). ROC analysis of the Cho/NAA ratio (n = 89) yielded an AUC of 0.858 (0.774–0.931); the exploratory, cohort-specific Youden-optimal cut-off was 1.41 (sensitivity 78.0%, specificity 87.2%). In the intention-to-diagnose analysis including all 99 examinations, accuracy was 78.8% (69.4–86.4). Diagnostic confidence increased significantly after ¹H-MRS (median 1 to 2; Wilcoxon p < 0.001; effect size r = 0.81), with moderate or major added value in 71 of 99 examinations (71.7%). Conclusions: In a diagnostically heterogeneous real-world cohort, ¹H-MRS significantly improved the accuracy achievable with conventional MRI alone and substantially increased reported diagnostic confidence, with high specificity but only moderate sensitivity. A zone-based Cho/NAA interpretative framework better reflects biological overlap than rigid binary thresholds. As this study assessed diagnostic accuracy and reported confidence rather than therapeutic decisions or patient outcomes, ¹H-MRS should be regarded as an adjunctive decision-support modality rather than a standalone classifier in routine neuro-oncologic workflows.