Improving Cancer Probability Estimation in Nondiagnostic Bronchoscopies: A Meta-Analysis

Background: In patients with peripheral pulmonary lesions (PPLs), nondiagnostic bronchoscopy results are not uncommon. The conventional approach to estimate the probability of cancer (pCA) after bronchoscopy relies on dichotomous test assumptions, using prevalence, sensitivity, and specificity to determine negative predictive value. However, bronchoscopy is a multidisease test, raising concerns about the accuracy of dichotomous methods.

Research question: By how much does calculating pCA using a dichotomous approach (pCA_dichotomous) underestimate the true pCA when applied to multidisease tests like bronchoscopy for the diagnosis of PPL?

Methods: In this meta-analysis of cohort studies involving radial endobronchial ultrasound for PPL, Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed, constructing 2 × 2 contingency tables for calculating pCA_dichotomous. For the multidisease test approach, 3 × 3 contingency tables for calculating probability of malignancy for a test that can have different categories of results and can diagnose multiple diseases (pCA_multidisease) using the likelihood ratio (LR) method for nondiagnostic results (LR(T0)) was used. Observed malignancy rates in patients with nondiagnostic results were compared with pCA_dichotomous and pCA_multidisease.

Results: In 46 studies (7,506 patients), malignancy was the underlying diagnosis in 76% of cases, another specific disease in 13% of cases, and nonspecific fibrosis or scar in 10% of cases. The percentage of patients with nondiagnostic results who had malignancy matched pCA_multidisease across all studies. In contrast, pCA_dichotomous consistently underestimated cancer risk (median difference, 0.12; interquartile range, 0.06-0.23), particularly in studies with a higher prevalence of nonmalignant disease. The pooled LR(T0) was 0.46 (95% CI, 0.40-0.52; I² = 76%; P < .001) and correlated with the prevalence of nonmalignant diseases (P = .001).

Interpretation: Conventional dichotomous methods for estimating pCA after nondiagnostic bronchoscopies underestimate the likelihood of malignancy. Physicians should opt for the multidisease test approach when interpreting bronchoscopy results.