Non-small cell lung cancer in ever-smokers vs never-smokers.

Background: Lung cancer is a leading cause of cancer-related mortality. Non-small cell lung cancer (NSCLC) comprises 85% of cases with rising incidence among never-smokers (NS). This study seeks to compare clinical, imaging, pathology, and outcomes between NS and ever-smokers (S) NSCLC patients to identify significant differences if any.

Methods: Retrospective cohort study of 155 NSCLC patients (88 S and 67 NS). The main predictor was smoking. Clinical, imaging, and pathology findings were evaluated at initial biopsy for staging. The primary outcome was all-cause mortality, and the secondary outcome was 12-month progression-free survival.

Results: Imaging: NS and S had similar nodule size (0.81), calcification (> 0.99), and invasion of adjacent structures (> 0.99) (p values). NS slightly trended to more commonly involve the RLL vs S the RUL (p = 0.11). NS had higher numbers of extrathoracic metastases at initial biopsy for staging (p = 0.055).

Pathology: NS more commonly had adenocarcinoma compared to S, who had equal numbers of adenocarcinoma and squamous cell carcinoma (p = 0.001). Rates of lymphovascular and pleural invasion were similar (p = 0.84 and 0.28). Initial staging: NS were more often initially diagnosed with stage IV disease (p = 0.046), positive nodal disease (p = 0.002), and metastatic disease (p = 0.004).

Outcomes: S had a non-significant trend toward worse 12-month progression-free survival (rate ratio = 1.31, p = 0.31; HR = 1.33, p = 0.28). NS and S had similar 1-year all-cause mortality (HR = 1.06, p = 0.90). S had nearly double the risk of all-cause mortality in 5 years (HR = 1.73, p = 0.056) and 10 years (HR = 1.77, p = 0.02). Median survival was 6.6 years for NS and 3.9 years for S, with NS surviving 2.7 years longer on average (p = 0.045).

Conclusions: CT nodule features were similar in NS and S. NS more often had metastatic adenopathy, distant metastases, and stage IV disease at initial biopsy. Despite similar 12-month progression-free survival and 1-year all-cause mortality, S had nearly double the risk of mortality in the first 5 and 10 years post-diagnosis.

Trial Registration: Retrospectively registered.