Impact of N1 lymph node burden on survival outcomes in non-skip pN2 non-small-cell lung cancer.

[OBJECTIVES] This study aimed to evaluate the prognostic value of quantitative N1 nodal burden metrics-including positive node count, positive station count, lymph node ratio (LNR), and lymph node station ratio (LNsR)-in patients with non-skip pN2 non-small cell lung cancer (NSCLC).

[METHODS] This retrospective study included 477 non-skip pN2 NSCLC patients who underwent complete surgical resection at our center from December 2008 to December 2020. N1 metrics were dichotomized based on optimal cutoffs determined by overall survival (OS). Kaplan-Meier analysis and Cox regression models were utilized to assess disease-free survival (DFS) and OS and to identify independent prognostic factors.

[RESULTS] In multivariable analysis, a high N1 LNR emerged as the sole N1 metric that independently predicted worse DFS (HR = 1.47, 95 % CI: 1.05-2.04, p = 0.023). In contrast, its prognostic significance for OS was attenuated (p = 0.162). However, an advanced pT4 stage (p = 0.044) was an independent predictor of worse OS, while adjuvant therapy (p = 0.016) was associated with improved OS. Notably, subgroup analysis revealed that an elevated N1 LNR independently predicted worse DFS in the pN2a subgroup (p = 0.009). Building on this, we developed a novel three-tiered stratification (pN2a-low LNR, pN2a-high LNR, and pN2b) that effectively discriminated patient outcomes for both DFS (p < 0.001) and OS (p < 0.01).

[CONCLUSIONS] N1 LNR is a powerful and independent predictor of disease recurrence in non-skip pN2 NSCLC, outperforming other N1 metrics for predicting DFS. Incorporating N1 LNR into clinical assessments, particularly for pN2a patients, can enhance prognostic accuracy and potentially guidemore personalized surveillance and treatment strategies.