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

Jeremy R. Burt, Naim Qaqish, Greg Stoddard, Amani Jridi, Parker Sage Anderson, Lacey Woods, Anna P. Newman, Malorie R. Carter, Reham Ellessy, Jordan Chamberlin, Ismail Kabakus

2025BMC Medicine15 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

MedicineInternal medicineAdenocarcinomaLung cancerLymphovascular invasionCancerStage (stratigraphy)OncologyRetrospective cohort studyBiopsyGastroenterologyPathologyMetastasisBiologyPaleontologyLung Cancer Diagnosis and TreatmentLung Cancer Treatments and MutationsGlobal Cancer Incidence and Screening