Not All T4 Patients Should Be Considered Equal: NSCLC Heterogeneity and Surgical Outcome

X. Luo¹, A. Hayanga¹, J. Lamb¹, J. Mehaffey¹, V. Badhwar¹, A. Seyfi. Toker^2
1West Virginia University, Morgantown, West Virginia ²West Virginia University, Department of Cardiovascular and Thoracic Surgery, Morgantown, West Virginia

Purpose: Current NSCLC staging considers T4 to include tumor size > 7cm, local invasion, or multifocal tumors in different ipsilateral lobes. Hence, T4 includes heterogeneous diseases with different oncologic biology, management, and surgical techniques. We hypothesize that subgroups of T4 NSCLC have different outcomes after surgical resection.

Methods: We used the National Cancer Database (NCDB) to examine NSCLC T4N0-2M0 patients who underwent surgical resection between 2010 and 2015. Patients were categorized by specific T4 characteristics (multifocal tumors, >7cm, and local invasion). We performed an effect modification analysis between T4 categories and nodal stage (N0-2) to evaluate differential association across nodal stages. Multivariable Cox regression was used to adjust for patient and tumor characteristics.

Results: A total of 14,239 patients with T4 NSCLC were identified. Multifocal tumors were noted in 3,472 (24.4%), 8,959 (62.9%) had tumor size > 7cm, and 1,808 (12.7%) had local invasion. After resection, multifocal tumors had the highest survival while local invasion had the lowest survival (Figure). The 5-year survival of patients with multifocal tumors, tumor size > 7cm, and local invasion tumors was 44.6%, 37.6%, and 31.7%, respectively. After adjustment, compared to multifocal tumors, tumors > 7cm were associated with 38% higher mortality (HR=1.38, 1.31-1.46, p< 0.001) and local invasion tumors were associated with 34% higher mortality (HR=1.34, 1.25-1.45, p< 0.001). The association differed significantly across nodal stages (Table). Among N0 disease, tumors > 7cm or local invasion had about 1.4 times mortality than multifocal tumors. With N1 disease, mortality of multifocal tumors increased to 1.48 times, and became similar to tumors > 7cm with N0 disease (HR=1.43) and local invasion with N0 disease (HR=1.40). With N2 disease, mortality of multifocal tumors increased to 1.80 times (HR=1.80) and became similar to tumors > 7cm with N1 disease (HR=1.82) and local invasion with N2 disease (HR=2.02). Tumors > 7cm with N2 disease had the highest mortality (HR=2.29).

Conclusion: In T4 patients with NSCLC, multifocal tumors had higher survival priority over tumor size or local invasion while the impact of nodal stage on survival varied by tumor class. The heterogeneity within T4 staging may provide opportunities for more targeted optimization of case selection and survival with surgical resection.

Identify the source of the funding for this research project: None