Survival patterns and mutation profiles in never- and light-smokers with stage IV NSCLC

Up to 15% of NSCLC cases arise in never-smokers, and an additional subset arises in light smokers. Data on these groups in the Middle East are limited. Therefore, we compared the clinicopathological features, survival, and molecular alterations in never and light smokers with stage IV NSCLC treated at a tertiary center in Jordan.

We retrospectively reviewed data from January 2015 to December 2023. Never-smokers were defined as those who had smoked < 100 lifetime cigarettes, and light smokers as those who had smoked < 5 pack-years. Survival rates and prognostic variables were estimated using Kaplan-Meier analysis and univariate Cox models.

Among 190 patients (median age 54 years), 159 were never smokers and 31 were light smokers. Never smokers were mainly female (69.8%), whereas light smokers were predominantly male (58.1%). Brain metastases were common (55.8%). EGFR mutations occurred in 80.6% of light smokers versus 58.5% of never-smokers. High PD-L1 expression (≥ 50%) was observed in 30% of both groups. One-year OS was 61% in never-smokers and 54.8% in light smokers. EGFR-negative tumors showed better 3- and 5-year OS than EGFR-positive tumors in both smoking strata. No clinical or molecular variables reached statistical significance in the univariate Cox analysis.

Never and light smokers with stage IV NSCLC displayed distinct features. The high prevalence of actionable EGFR alterations underscores the importance of comprehensive molecular testing. Region-specific data should inform precision oncology strategies and the design of prospective trials targeting non-traditional risk groups.