Abstract
Lung cancer is the leading cause of cancer-related deaths in the US, predominantly non-small cell lung cancer (NSCLC). Lymph node metastasis significantly impacts prognosis, yet current classification systems lack precision. Lymph node ratio (LNR), correlating metastatic to total lymph nodes, emerges as a superior prognostic tool. The study aimed to identify statistically validated LNR cutoffs and evaluate their prognostic significance in NSCLC patients, addressing limitations in the current tumor, node, and metastasis staging system. The study utilized data from the surveillance, epidemiology, and end results database (2010-2019) to analyze NSCLC patients undergoing tumor excision. Exclusions included those receiving chemotherapy or radiotherapy. Patients receiving chemotherapy or radiotherapy were excluded to isolate the independent impact of surgical lymph node retrieval on cancer-specific survival. The primary outcome focused on cancer-specific survival (CSS) stratified by LNR, with secondary analysis on N1/N2 NSCLC cases. X-tile software determined LNR cutoffs, categorizing patients into 3 groups. Descriptive statistics and Kaplan-Meier analysis were employed, along with multivariate Cox regression. Lower Akaike information criterion (AIC) values favored LNR models. Empower Stats and R software were utilized, with P < .05 indicating significance. Median CSS follow-up was 22 months, with 1265 NSCLC-related deaths. Lymph node retrieval averaged 11, with a median LNR of 0.15. X-tile analysis revealed LNR thresholds of 0.17 and 0.34, stratifying patients into low, medium, and high-risk groups. Kaplan-Meier show better differentiation when LNR is used as a predictor compared to N staging (LNR P < .0001 vs N stage P = .91). Multivariate Cox regression confirmed high LNR as an independent predictor of poorer CSS. A lower Akaike information criterion for LNR models highlighted its superior prognostic accuracy over N staging. This study demonstrates that the LNR is a superior prognostic indicator for N1 and N2 stage NSCLC compared to traditional N staging. By integrating metastatic burden and lymph node retrieval extent, LNR addresses key gaps in the tumor, node, and metastasis system and provides enhanced risk stratification. Clinicians can use LNR to identify high-risk patients who may benefit from intensified adjuvant therapies or tailored follow-up protocols. Further prospective studies are warranted to establish standardized LNR thresholds and validate its integration into clinical practice.