Abstract
BACKGROUND: Unsuspected (defined here as occult) N2-positive lung cancer impacts overall survival (OS), and treatment patterns likely influence outcomes. We aimed to evaluate factors that could improve the long-term outcomes of patients with occult N2 disease compared to biopsy-proven, pre-resectional N2 disease. METHODS: Our institutional prospective database was queried for N2 non-small cell lung cancer (NSCLC) at presentation (biopsy-proven) prior to surgical resection or postoperatively diagnosed N2 (occult N2), excluding stage IV disease or patients with insufficient follow-up. In occult N2 group, postoperative therapy was stratified into complete (≥3 cycles), incomplete (1-2 cycles), or no adjuvant treatment. Propensity score weighting adjusted for age, comorbidities, tumor size, and N2 involvement. Kaplan-Meier analysis assessed 5-year overalls survival (OS). RESULTS: Between 2006-2023, 483 patients met inclusion criteria, stratified into 325 patients (67.2%) with biopsy-proven N2 and 158 (32.8%) with occult N2. The biopsy-proven N2 group primarily received neoadjuvant therapy (chemo/chemoimmunotherapy ± radiation). In the occult N2 group, 86 patients (54.4%) received full-dose adjuvant therapy, 31 (19.6%) received incomplete adjuvant therapy, and 41 (26%) received no adjuvant therapy. After propensity score weighting, the occult N2 group had significantly lower OS (P = .03); however, when the cohort was stratified by completeness of adjuvant treatment, those who received full adjuvant therapy had OS comparable to that of the biopsy-proven group (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.65-1.48; P = .9). Incomplete therapy provided some survival benefits but was associated with worse OS compared to complete therapy (HR, 1.54; 95% CI, 0.9-2.6; P = .1). The no-therapy group had the lowest OS. CONCLUSIONS: Patients with occult N2 treated with adjuvant treatment may achieve improved survival rates compared to those not fully treated. Neoadjuvant treatment is optimal to ensure delivery of therapy as prescribed, and thus every effort should be made to identify N2 disease prior to resection.