Abstract Rationale Accurate mediastinal staging is critical in operable lung cancer to guide appropriate treatment decisions. While positron emission tomography/computed tomography (PET/CT) is commonly used as an initial modality, its limitations in detecting small or low-metabolic lymph nodes may lead to under-staging. Endobronchial and/or endoscopic ultrasound (EBUS/EUS) enables nodal sampling for cytological confirmation, however is not routinely used in PET/CT-negative disease. We aimed to quantify the added diagnostic value of EBUS/EUS following PET/CT in mediastinal staging of operable lung cancer. Methods We conducted a systematic review and meta-analysis (PROSPERO CRD42024553195). PubMed, EMBASE, Scopus, and the Cochrane Library were searched for studies from January 1, 2000, to July 1, 2025. Eligible studies included treatment-naive operable lung cancer patients who underwent mediastinal staging using both PET/CT and EBUS/EUS, with verification by a reference standard. Exclusion criteria included advanced-stage disease, restaging, absence of nodal status data, or insufficient information to construct 2 × 2 diagnostic tables. Two reviewers independently extracted data and assessed study quality using the QUADAS-2 and QUADAS-C tools. Pooled sensitivity, specificity, accuracy, and diagnostic odds ratios (DOR) were calculated using the random-effects model. The heterogeneity was evaluated using I² statistic. Results Of 7,198 citations, 32 studies (n = 4,162) were included. The mean age of participants ranged from 52.4 to 67.9 years, with 67.6% being male. Among the included studies, 25 were single-centre, and 18 were retrospective. PET/CT positivity was variably defined, ranging from visual assessment (e.g., FDG uptake greater than background) to specific SUV thresholds (2.5, 3.0, 4.5). Sixteen studies included a staging spectrum from cN0 to cN3, while others restricted enrolment to PET/CT-negative cN0 or cN1 cases. EBUS alone was performed in 18 studies, EUS in 4, and both combined in 10. Reference standards included EBUS/EUS cytology, histology, and surgery (resection, lymph node dissection/biopsy), with clinical/radiological follow-up in some studies. EBUS/EUS following PET/CT showed higher pooled sensitivity (70·9% 95% CI: 61·7-81·5) and specificity (99·9% 99·7-100) than PET/CT alone (sensitivity 25·7% 14·9-44·4; specificity 85·4% 78·5-92·8). Pooled accuracy increased from 79·2% to 94·3%. DOR increased from 7·2 to 290·2. EBUS/EUS upstaged 6·3% and downstaged 7·7% of patients. I² for sensitivity and accuracy exceeded 80%, indicating heterogeneity. GRADE certainty for EBUS/EUS was moderate for specificity and low for sensitivity. Conclusion EBUS/EUS substantially improves staging accuracy after PET/CT, even in cases where PET/CT is negative. These findings support broader use of EBUS/EUS beyond current guideline indications. However, limitations include significant heterogeneity and publication bias. This abstract is funded by: None
Damaraju et al. (Fri,) studied this question.