Chemotherapy and Surgical Resection for N1 Positive Non-small Cell Lung Cancer: Better Than Expected Outcomes

N1-positive (T1-3, N1, M0) non-small cell lung cancer (NSCLC) represents a minority distribution (∼8%) of the approximately 234,000 diagnosed cases per year. As such, there is a paucity of modern high-quality data regarding outcomes following surgically-resected, stage N1-positive NSCLC. Randomized controlled trials from more than a decade ago have demonstrated a modest 5.4% survival benefit with adjuvant chemotherapy but have included heterogenous patient populations and stage distributions. Large database analyses have questioned the role of perioperative chemotherapy in resected patients with N1 disease, but without much granular detail regarding staging, quality of surgery, and chemotherapy. This single-institution study sought to evaluate the role of perioperative chemotherapy, specifically in N1-positive NSCLC patients. Data for all patients with surgically resected N1-positive NSCLC (T1-3, N1, M0) between 2006 and 2016 were collected for this study. Patients who underwent pneumonectomy were excluded from analysis. A retrospective chart review was conducted, and comprehensive clinicopathologic data were collected relative to staging, surgery, pathologic review, and perioperative oncology treatment. After exclusion criteria were applied, 148 patients with surgically resected, N1-positive disease (T1-3, N1, M0) remained for analysis. The majority of patients underwent lobectomy (75.0%), of which 55.4% underwent minimally invasive resection. There were no differences in postoperative complications, length of stay, number of lymph nodes sampled, or mortality associated with the surgery only and surgery with adjuvant therapy subgroups. 107 patients (72.3%) received adjuvant therapy, and this was associated with higher 5-year overall survival (62.8%) and disease-free survival (45.1%) than patients who underwent surgery only (33.9% overall survival at 5 years, P = 0.01; 22.4% disease-free survival at 5 years, P = 0.04). The presence of multistation N1 nodal metastases in patients was associated with lower 5-year overall survival (22.7%) and disease-free survival (5.6%) than patients with single-station N1 nodal metastasis (60.4% overall survival at 5 years, P = 0.003; 46.0% disease-free survival at 5 years, P < 0.001). On multivariable analysis, receiving any adjuvant chemotherapy was associated with improved overall survival and disease-free survival (Overall Survival HR 0.47, P < 0.01 | Disease-Free Survival HR 0.46, P <0.01). Multistation N1 disease was associated with significantly worse disease-free survival (HR 2.11, P = 0.04). Perioperative chemotherapy was associated with improved survival in N1-positive NSCLC, and the potential magnitude of benefit exceeded 25% in this study. Patients with single-station N1 lymph node metastasis were observed to have better disease-free survival.