BackgroundIn patients with peripheral pulmonary lesions (PPL), non-diagnostic bronchoscopy, results are not uncommon. The conventional approach to estimate the probability of cancer (pCA) following bronchoscopies relies on dichotomous test assumptions, utilizing prevalence, sensitivity, and specificity to determine negative predictive value (NPV). However, bronchoscopy is a multi-disease test, raising concerns about the accuracy of dichotomous methodologies. Research QuestionBy how much does calculating pCA using a dichotomous approach (pCAdichotomous) underestimate the true pCA when applied to multi-disease tests like bronchoscopy for the diagnosis of PPL? MethodsMeta-analysis of cohort studies involving radial-EBUS for PPL. PRISMA guidelines were followed, constructing 2×2 contingency tables for calculating pCAdichotomous. For the multi-disease test approach, 3×3 contingency tables for calculating pCAmulti-disease using the likelihood ratio method for non-diagnostic results LR(T0) was used. Observed malignancy rates in patients with non-diagnostic results were compared to pCAdichotomous and pCAmulti-disease. ResultsIn 46 studies (7506 patients), malignancy was the underlying diagnosis in 76%, another specific disease in 13%, and non-specific fibrosis/scar in 10%. The percentage of patients with non-diagnostic results who had malignancy matched pCAmulti-disease across all studies. In contrast, pCAdichotomous consistently underestimated cancer risk (median difference: 0.12, 25th−75th percentile: 0.06−0.23), particularly in studies with a higher prevalence of non-malignant disease. The pooled LR(T0) was 0.46 (95% CI 0.40−0.52, I2 76%, p<0.001), and correlated with the prevalence of non-malignant diseases (p=0.001). InterpretationConventional dichotomous methods for estimating pCA after non-diagnostic bronchoscopies underestimate the likelihood of malignancy. Physicians should opt for the multi-disease test approach when interpreting bronchoscopy results.