Abstract 734: Comprehensive validation of high-risk clinicopathologic features in early-stage, node-negative non-small cell lung cancer
Authors: Heiden Brendan T. , Eaton Daniel B. , Chang Su-Hsin , Yan Yan , Schoen Martin W. , Patel Bindiya G. , Thomas Theodore S. , Meyers Bryan F. , Kozower Benjamin D. , Puri Varun 
Published: April 2023

Abstract
Objective: Current guidelines recommend adjuvant therapy for patients with completely resected non-small cell lung cancer (NSCLC) with high-risk clinical or pathologic features. Despite this, the relationship between these features and cancer recurrence is poorly elucidated.
Methods: We conducted a retrospective cohort study using a uniquely compiled dataset from the US Veterans Health Administration (VHA) including all Veterans with pathologic early-stage (≤5cm, N0) NSCLC receiving definitive surgical treatment (2010-2016). Based on National Comprehensive Cancer Network guidelines, we evaluated 6 high-risk features: tumor size, tumor grade, visceral-pleural invasion, lymphovascular invasion, non-anatomic wedge resection, and adequacy of nodal sampling. We developed a score reflecting the relationship between these high-risk features and recurrence, using a multivariable competing risk model (death as competing event). The score performance was then tested in an external cohort from the National Cancer Database (NCDB).
Results: The study included 3,799 Veterans. The median follow-up was 7.1 years. Recurrence was detected in 800 (21.1%) patients. The association between high-risk features and cancer recurrence were as follows: tumor size (e.g., 31-40mm vs. 0-10mm, multivariable-adjusted hazard ratio, aHR 1.676, 95% CI 1.229-2.285, p=0.001), tumor grade (e.g., III vs. I, aHR 1.884, 95% CI 1.448-2.449, p&lt;0.001), visceral-pleural invasion (aHR 1.096, 95% CI 0.905-1.329, p=0.35), lymphovascular invasion (aHR 1.747, 95% CI 1.441-2.117, p&lt;0.001), non-anatomic wedge resection (aHR 1.335, 95% CI 1.101-1.619, p=0.003), and adequacy of nodal sampling (e.g., 1-4 lymph nodes vs. ≥10 lymph nodes, aHR 1.392, 95% CI 1.149-1.687, p&lt;0.001). Using these parameters, a score was created reflecting the association between high-risk features and recurrence. The score ranged from 0-36, with higher scores reflecting higher cumulative incidence of recurrence. The score was further divided into low- (0-11, n=1,263, 33.3%; 5-yr recurrence risk 13.0%), moderate- (12-15, n=1,134, 29.9%; 5-yr recurrence risk 19.0%), and high-risk (16-36, n=1,402, 36.9%; 5-yr recurrence risk 27.1%) categories. Higher scores were also associated with diminished overall survival (median OS, low-risk: 9.0 yrs; moderate-risk: 7.3 yrs; high-risk: 5.4 yrs). The score was further tested in a cohort of 63,232 patients from the NCDB and higher scores remained associated with worse overall survival (median OS, low-risk: 9.4 yrs; moderate-risk: 8.0 yrs; high-risk: 6.3 yrs).
Conclusions: High-risk clinicopathologic features are associated with dramatically higher risk of recurrence and worse overall survival. Multivariable assessment of these features using a comprehensive yet pragmatic score may help to standardize adjuvant treatment eligibility following curative intent resection.
Citation Format: Brendan T. Heiden, Daniel B. Eaton, Su-Hsin Chang, Yan Yan, Martin W. Schoen, Bindiya G. Patel, Theodore S. Thomas, Bryan F. Meyers, Benjamin D. Kozower, Varun Puri. Comprehensive validation of high-risk clinicopathologic features in early-stage, node-negative non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 734.