P1.03-066 Incorporation of a Molecular Prognostic Classifier Improves Conventional Non-Small Cell Lung Cancer TNM Staging

Abstract

Tumor size, nodal spread, and distant metastases form the basis of current non-small cell lung cancer staging. Despite undergoing a major revision in 2009, the poor outcomes of early-stage lung cancer patients relative to other solid tumors such as breast and colorectal cancer suggests that further improvement to our ability to stage non-small cell lung cancers is needed. In this study, we demonstrate the benefit of integrating a clinically validated molecular prognostic signature into conventional TNM staging. A new staging system integrating a 14-gene molecular prognostic classifier with TNM descriptors was developed using 332 patients with stage I-IIIB non-squamous, non-small cell lung cancer resected at the University of California, San Francisco. This staging system was subsequently validated on a separate multi-institutional international cohort of 1379 patients with stage I-IIIB disease. Reclassification measures were used to assess for improvements in calibration and discrimination beyond conventional TNM staging. In the validation cohort, 78.2% of patients were reclassified using the new staging system. 73% of these patients were reclassified more accurately. The new staging system demonstrated improved measures of model fit including the modified Nagelkerke’s R2 statistic as well as the c-index. In addition, incorporation of the molecular classifier resulted in a Net Reclassification Improvement of 16.6% (95% CI 7.9-25.2%) and a relative Integrated Discrimination Improvement of 27.9% (95% CI 6.4-49.4%). Kaplan-Meier analysis of overall survival after surgical resection demonstrated superior survival curve separation with the addition of the molecular classifier. Incorporation of a molecular classifier of tumor biology offers substantial improvements to conventional TNM staging and encourages application of molecular prognostic classifiers into the refinement of TNM staging systems for other solid tumors.