B80-4-05 Real-world Community Experience Using Blood-Based Nodify Classifiers (CDT and XL2) For Lung Nodule Risk Stratification

Background Solitary pulmonary nodules ≥8 mm often present a diagnostic dilemma in community settings, where access to advanced imaging and interventional procedures may be limited. Blood-based classifiers—Nodify CDT (autoantibody test detecting tumor-associated antigens) and Nodify XL2 (plasma proteomic classifier) offer a non-invasive method to refine malignancy risk and guide management decisions. Nodify CDT results are categorized as High, Moderate, or NSLAD (No Significant Level of Autoantibody Detection). We evaluated their real-world performance and workflow impact within a community lung-nodule program. Methods Patients with solid or subsolid nodules ≥8 mm and no prior malignancy were prospectively evaluated in a multidisciplinary lung-nodule clinic. All underwent Nodify CDT ± XL2 testing. Management (CT surveillance, biopsy, or resection) was guided by test results and imaging findings. Outcomes were confirmed by pathology or ≥ 12-month radiographic stability. Patients with CDT High or Moderate results were triaged for expedited biopsy or resection within the same clinic cycle, while low-risk results (NSLAD or XL2 Reduced Risk) were directed to imaging surveillance. Primary endpoints included malignancy rate by test category, PET correlation, and biopsy-rate reduction compared with a pre-implementation baseline (∼45 %). Results Among 54 patients (mean age 68 years; 53 % female; 61 % current/former smokers): CDT: High/Moderate (n = 7) → malignant 75 %; NSLAD (n = 47) → 11 % malignant. XL2: Reduced Risk (n = 21) → 95 % benign; Likely Benign (n = 16) → 81 % benign; Indeterminate (n = 9) → 11 % malignant. Workflow: Surveillance 63 % (34/54); Biopsy 26 % (14/54); Resection 11 % (6/54). Biopsy rate declined from 45 % → 26 % (absolute reduction ≈ 19 %; NNT ≈ 4-5). All CDT High/Moderate patients underwent tissue diagnosis, most within the first clinic cycle, reflecting accelerated triage for higher-risk results. PET Accuracy: Avid = 100 % sensitivity, 37 % specificity, PPV 28 %, NPV 100 %. CDT Accuracy: High/Moderate = 50 % sensitivity, 95 % specificity, PPV 71 %, NPV 89 %. Clinical Implications: PET: Highly sensitive but low specificity; excellent rule-out test for malignancy. CDT: High specificity and PPV; effective rule-in tool for malignancy. Combined workflow: Sequential CDT → PET approach may maximize diagnostic precision while minimizing unnecessary interventions. Implementation of these classifiers safely down-classified solitary pulmonary nodules, enabled confident surveillance in two-thirds of patients, and reduced invasive procedures by ≈ 20-25 %. This model demonstrates that molecular risk stratification can be effectively applied beyond tertiary centers, improving diagnostic accuracy and workflow efficiency in community practice.