Upfront surgery for N2 NSCLC: a large retrospective multicenter cohort study

Background: The optimal sequence and combination of surgery, chemotherapy and radiotherapy in patients with N2 non-small cell lung cancer (NSCLC) remain undefined. The aim of our study was to compare two treatment options for N2 NSCLC—induction therapy with subsequent surgery versus upfront surgery with adjuvant treatment. Methods: We retrospectively reviewed 405 patients with N2 disease in two centers, between January 2010 and December 2016. They were divided into two groups: the Induction Group, composed of patients who received neoadjuvant chemotherapy, and the Upfront surgery Group, composed of patients who underwent surgery as first-line therapy. Propensity score-matched (PSM) analysis was performed, and 52 patients were included in each group. Primary endpoints were: recurrence, overall survival (OS) and disease-free survival (DFS). Results: After the PSM, no differences were observed in general characteristics, perioperative results, rates and severity of complications, and histopathology results. Seventeen patients (32.7%) of the induction group and 21 (40.4%) of the upfront surgery group had mediastinal lymph nodal involvement with skipping (p = 0.415). Recurrence rate was not different between the two groups (57.7% vs 50.0%, p = 0.478). No differences were observed in terms of OS (40.98 ± 35.78 vs 37.0 ± 40.69 months, p = 0.246) and DFS (29.67 ± 36.01 vs 27.96 ± 40.08 months, p = 0.697). The multivariable analysis identified the pT stage and skipping lymph node metastasis as independent predictive factors for OS. Conclusions: Upfront surgery followed by adjuvant therapy does not appear inferior in terms of recurrence, OS and DFS, compared to induction chemotherapy with subsequent surgery.