The critical role of accurate neoplastic cell percentage (NCP) assessment: investigating targeted training strategies for pulmonary biopsy and cytology specimens.

Cancer diagnostics and therapeutics have widely changed, and in advanced non-small cell lung cancer (aNSCLC), molecular analysis is crucial to identify actionable biomarkers. Targeted therapies specifically interfere with molecular mechanisms involved in tumor growth and proliferation to improve clinical outcomes and quality of life compared to conventional chemotherapy. However, suboptimal testing practices, including errors in neoplastic cell percentage (NCP) assessment, limit reliable downstream analyses, and therefore, hinder accurate targeted therapy decisions for NSCLC patients. This study conducted two assessment rounds in which participants evaluated cytology or biopsy cases to examine NCP assessment accuracy and molecular testing decisions among pathologists and non-pathologists. No evidence was found for changes in NCP assessment performance across rounds (OR = 1.996, 95% CI = [0.600;6.644], p = 0.260) and they were also not influenced by professional background (OR = 0.932, 95% CI = [0.611;1.421], p = 0.743). However, prior training in NCP assessment showed potential benefit for accurate NCP estimation. Additionally, incorrect NCP assessments were significantly linked to subsequent molecular testing decision errors (OR = 2.327, 95% CI = [1.286;4.212], p = 0.005), and the inter-observer agreement for cytology cases was poor with higher error rates for cytology cases compared to biopsy cases (OR = 2.389, 95% CI = [0.967;5.906], p = 0.059). In conclusion, a continuing need for training focusing on harmonization of NCP assessment and molecular testing decision-making remains. Ultimately, such assessment improvements will enhance accuracy of downstream precision medicine for NSCLC patients.