Role of Pathologic Single-Nodal and Multiple-Nodal Descriptors in Resected Non-Small Cell Lung Cancer

Background: The eighth edition of lung cancer nodal staging assignment includes the location of lymph node metastasis, but does not include single-nodal and multiple-nodal descriptors. Research Question: Do the single-nodal and multiple-nodal statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and Methods: Using the National Cancer Database, we analyzed patients with pathologically staged N1 and N2 NSCLC. Nodal descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pathological single N2 (pSingle-N2), and pathological multiple N2 (pMulti-N2). Survival analysis was performed using the Kaplan-Meier method and multivariable Cox regression models. Results: In the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 patients with NSCLC demonstrated pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2 disease, respectively. Patients with pMulti-N1 and pMulti-N2 disease showed a shorter survival than those with pSingle-N1 and pSingle-N2 disease, respectively (hazard ratio, 1.22 [P <.0001] for N1 and 1.39 [P <.0001] for N2). After adjusting age, sex, and histologic findings, the hazard ratio for pSingle-N2 compared with pMulti-N1 disease was 1.05 (P =.0031). Patients with pN1 disease were categorized by metastatic lymph node count (1, 2, 3, ≥ 4), showing significant prognostic differences among groups (P <.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy, or more; survival ≥ 30 days; ≥ 10 examined lymph nodes; and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708), analyses supported these results. Interpretation: Patients with NSCLC with one metastatic lymph node, whether in N1 or N2 stations, showed better survival than those with more than one lymph node involved. Patients with NSCLC with a single-skip N2 lymph node metastasis showed survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to four or more was sequentially prognostic.