Surgical Approach and Prognosis in Patients with ≤2 cm Grade 3 Lung Adenocarcinoma: A Multivariable Analysis of Disease-Free and Overall Survival

Background: High-grade histological patterns are established risk factors for poor prognosis in lung adenocarcinoma. Whether sublobar resection is oncologically equivalent to lobectomy in ≤2 cm grade 3 lesions remains unclear. This study compared the effects of different surgical approaches on perioperative outcomes and long-term survival.

Methods: We retrospectively reviewed 239 patients who underwent curative-intent resection for grade 3 invasive lung adenocarcinoma ≤2 cm between January 2014 and December 2023. Patients were stratified into lobectomy (n=121), segmentectomy (n=74), and wedge resection (n=44) groups. Perioperative and oncological outcomes were compared among the three groups. Inverse probability of treatment weighting (IPTW) and weighted Cox models were used to compare survival. Multivariable analysis was performed using Firth's penalized Cox regression.

Results: No significant differences were observed in preoperative characteristics among the three groups ( P > 0.05).Significant differences were observed in operative time among the three groups (P = 0.003). The wedge resection group had the shortest operative time and the least blood loss, whereas the lobectomy group had the longest operative time and the greatest blood loss.Postoperative pathological features, including high-grade patterns proportion, spread through air spaces (STAS), perineural invasion (PNI), lymphovascular invasion (LVI), and TNM stage, were comparable across groups (P > 0.05). However, lobectomy was associated with significantly greater numbers of dissected lymph node stations (P < 0.001) and total lymph nodes retrieved (P = 0.015).After IPTW adjustment, the 5-year DFS rates were 85.6%, 84.7%, and 58.4%, respectively; the weighted log-rank test showed a significant difference (P = 0.027), with wedge resection associated with significantly worse DFS versus lobectomy (weighted HR 2.53; 95% CI 1.21–5.28; P = 0.014), whereas segmentectomy was comparable (weighted HR 1.05; 95% CI 0.46–2.41; P = 0.902). The 5-year overall survival (OS) rates were 85.7%, 89.3%, and 82.8%, respectively, with no significant intergroup difference (χ² = 0.442, P = 0.802).Multivariable Firth analysis identified preoperative carcinoembryonic antigen (CEA) positivity (HR 2.60, 95% CI 1.27–5.11, P = 0.010) and tumor size > 10 mm (HR 3.56, 95% CI 1.31–13.35, P = 0.010) as independent risk factors for DFS.Micropapillary component of ≥5% was an independent risk factor for OS (HR 3.92, 95% CI 1.57–11.73, P = 0.003).Although surgical approach was not significantly associated with OS (P = 0.470), wedge resection emerged as a borderline unfavorable risk factor for worse DFS (HR 2.03, 95% CI 0.99–3.95; P = 0.054).

Conclusions: In patients with ≤2 cm high-grade lung adenocarcinoma, segmentectomy demonstrated comparable long-term survival to lobectomy. Wedge resection, however, showed an unfavorable trend in 5-year DFS rate and should be cautiously selected.