Smoking History Predicts for Increased Risk of Second Primary Lung Cancer: A Comprehensive Analysis

BACKGROUNDTobacco use is the most important risk factor for the development of lung cancer. The objective of the current study was to determine the effect of smoking on the development of second primary lung cancers (SPLCs) and other clinical outcomes after surgery for non-small cell lung cancer (NSCLC). METHODSAll patients who underwent surgery for NSCLC at the study institution from 1995 through 2008 were identified. Rates of SPLC were analyzed based on smoking status and pack-year exposure. Multivariate analysis was performed to determine risk factors for SPLC. Overall survival, local control, distant metastases, and postoperative mortality were also examined. RESULTSA total of 1484 patients were identified, including 98 never-smokers. The incidence of SPLC at 3 years, 5 years, and 8 years was 5%, 8%, and 16%, respectively. Only 1 never-smoker developed an SPLC. On multivariate analysis, which was restricted to ever-smokers with pack-years as a continuous variable, smoking history was found to be the only independent risk factor for SPLC (hazard ratio, 1.08; 95% confidence interval, 1.02-1.16 [P=.031]), corresponding to an 8% increased risk per 10 pack-year exposure. There were no differences in rates of local control or distant metastases based on smoking status. There was a trend toward lower postoperative mortality in never-smokers compared with ever-smokers (0% vs 3.3%; P=.069). Overall survival was found to be significantly worse for current smokers compared with former and never-smokers. CONCLUSIONSSPLCs are rare in never-smokers. Increasing tobacco exposure is associated with a higher risk of SPLC in patients with a history of smoking. Current smokers have an increased risk of mortality whereas former and never-smokers have comparable survival. Cancer 2015;121:598-604. (c) 2014 American Cancer Society. The current study identifies and quantifies risk factors for second primary lung cancer in a population of patients treated for an index non-small cell lung cancer. Among 1484 subjects, it was found that smoking was the only risk factor assessed that predicted for the development of a second primary lung cancer, with never-smokers having an exceedingly low risk.