Introduction: The importance of identifying non-small cell lung cancer (NSCLC) histologic subtype has increased recently because of the development of target-specific chemotherapeutic agents. This systematic review was undertaken to examine the interobserver variability for histology in differentiating between subtypes of NSCLC, specifically the ability to differentiate squamous from nonsquamous histology.
Methods: A systematic literature search was undertaken to identify studies that evaluated the reproducibility of histologic diagnosis by pathologists in their reporting of NSCLC subtypes. Studies were screened using a priori defined eligibility criteria. The National Health and Medical Research Council diagnostic levels of evidence were applied and quality assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Data were extracted and reanalyzed to permit comparison of agreement in nonsquamous and squamous cell carcinoma by 2 × 2 tables. Percentage agreement and kappa statistics were calculated for each included study.
Results: Out of 1480 articles identified through the literature search, six were eligible for inclusion. The percentage agreement for all subtypes of NSCLC in the included studies ranged from 67.1 to 89.6% (κ, 0.42-0.84). Based on the primary reanalysis of data (reanalysis 1), agreement between pathologists in differentiating nonsquamous and squamous histology ranged from 77.0 to 94.2% (κ = 0.48-0.88) indicating a moderate to high level of agreement.
Conclusion: The reasonably high agreement and kappa statistics for the included studies suggest that pathologists can reproducibly differentiate between nonsquamous and squamous NSCLC. This is clinically important in guiding oncologist decision making in choosing the most appropriate therapy for their patients.