Prognostic significance of different lymph node staging systems in patients with resectable, node-positive, stage III, non-small cell lung cancer: Identifying the optimal classification for enhanced prognostic stratification.

Purpose: The traditional N staging system fails to adequately stratify the prognostic heterogeneity in patients with resectable node-positive, stage III, non-small cell lung cancer, particularly in those undergoing postoperative radiotherapy. The purpose of this study was to determine the optimal nodal status classification strategy: the traditional N classification, the positive lymph nodes-based classification, or the lymph node ratio-based classification. Furthermore, we aimed to identify the population that would benefit the most from postoperative radiotherapy using the best classification strategy.

Methods: We analysed data from 5028 patients with resectable node-positive, stage III, non-small cell lung cancer sourced from the Surveillance, Epidemiology, and End Results (SEER) database. Various lymph node staging systems, including traditional N staging, classification based on the number of positive lymph nodes, and classification based on the lymph node ratio, were incorporated into the prognostic prediction model. Survival outcomes were evaluated using lung cancer-specific survival and Kaplan-Meier analysis.

Results: The lymph node ratio classification model demonstrated the highest prognostic prediction performance, with the highest C-index, area under the curve, and the lowest Akaike information criterion, followed by the positive lymph nodes classification model and the traditional N staging model. Prognostic stratification analysis based on different lymph node staging systems indicated that a lymph node ratio greater than 0.28 and more than three positive lymph nodes were associated with a high-risk prognosis. Furthermore, postoperative radiotherapy significantly improved lung cancer-specific survival in overall resectable node-positive, stage III, non-small cell lung cancer (P<0.05). Notably, survival curve analysis revealed the most pronounced differences in lung cancer-specific survival between the groups receiving postoperative radiotherapy or not in the high-risk prognosis group, particularly among those with a lymph node ratio greater than 0.28, and more than three positive lymph nodes, and lastly the traditional N staging model.

Conclusion: In patients with resectable node-positive, stage III, non-small cell lung cancer, classification according to the lymph node ratio, followed by the positive lymph nodes, may offer superior prognostic prediction capabilities compared to the traditional N staging in addressing prognostic heterogeneity. Additionally, identifying a high-risk prognosis with a lymph node ratio greater than 0.28 appears to be the most effective criterion for selecting candidates who would benefit from postoperative radiotherapy.