Assessment of Plasma Proteomics Biomarker’s Ability to Distinguish Benign From Malignant Lung Nodules: Results of the PANOPTIC (Pulmonary Nodule Plasma Proteomic Classifier) Trial

Background Lung nodules are a diagnostic challenge, with an estimated yearly incidence of 1.6 million in the United States. This study evaluated the accuracy of an integrated proteomic classifier in identifying benignnodules in patients with a pretest probability of cancer (pCA) ≤ 50%. Methods A prospective, multicenter observational trial of 685 patients with 8- to 30-mm lung nodules was conducted. Multiple reaction monitoring mass spectrometry was used to measure the relative abundance of two plasma proteins, LG3BP and C163A. Results were integrated with a clinical risk prediction model to identify likely benignnodules. Sensitivity, specificity, and negative predictive value were calculated. Estimates of potential changes in invasive testing had the integrated classifier results been available and acted on were made. Results A subgroup of 178 patients with a clinician-assessed pCA ≤ 50% had a 16% prevalence of lung cancer. The integrated classifier demonstrated a sensitivity of 97% (CI, 82-100), a specificity of 44% (CI, 36-52), and a negative predictive value of 98% (CI, 92-100) in distinguishing benignfrom malignant nodules. The classifier performed better than PET, validated lung nodule risk models, and physician cancer probability estimates ( P Conclusions When used in patients with lung nodules with a pCA ≤ 50%, the integrated classifier accurately identifies benignlung nodules with good performance characteristics. If used in clinical practice, invasive procedures could be reduced by diverting benignnodules to surveillance. Trial Registry ClinicalTrials.gov; No.: NCT01752114; URL: www.clinicaltrials.gov).