Clinical stage-specific prognostic impact of adequate lymphadenectomy in early-stage lung cancer

To assess the prognostic impact of adequate lymphadenectomy and determine the optimal nodal assessment for different clinical stages of lung cancer.

We retrospectively reviewed 1214 patients with clinical stage I-III non-small cell lung cancer who had preoperative positron emission tomography/computed tomography and curative surgery (2006-2017). Patients were categorized based on whether they had adequate (R0) or inadequate lymphadenectomy [R(un)]. Propensity score matching was conducted to minimize bias. Primary end points were recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival. Secondary end points included outcomes stratified by clinical stages.

Multivariate Cox analysis identified preoperative carcinoembryonic antigen level, tumour size, uptake of tumour on positron emission tomography/computed tomography, R(un) [hazard ratio (HR) = 2.16; P < 0.001), angiolymphatic invasion, lymph node involvement and postoperative adjuvant therapy as independent predictors of RFS. The matched cohort included 440 R0 and 440 R(un) patients, with a median follow-up of 94 months. Significant differences were found in 10-year RFS (77.2% vs 61.3%, P < 0.001), OS (75.8% vs 64.3%, P < 0.001) and cancer-specific survival (83.8% vs 74.2%, P < 0.001). Despite longer operative time for R0 (210 vs 195 min, P = 0.008), perioperative complications, hospital stay length and blood loss were similar. Subgroup analysis showed R(un) as an independent predictor of RFS in clinical stages IA3 (HR = 2.53, P = 0.001), IB (HR = 1.71, P = 0.046), and II (HR = 2.44, P < 0.001), but not in IA1 or IA2. R0 had significantly better RFS than R(un) in matched cohort of stages IA3 (P = 0.003), IB (P = 0.001) and II (P = 0.001).

Adequate lymph node assessment improves prognosis in patients with clinical stages ≥ IA3. A uniform nodal assessment approach should be reconsidered for different clinical stages.