The Impact of Cigarette Smoking on Prognosis in Small Adenocarcinomas of the Lung: The Association Between Histologic Subtype and Smoking Status

ObjectiveIn this retrospective study, we clarified the impact of smoking on prognosis and the association of clinicopathological factors, particularly histologic subtype, in patients with small adenocarcinoma of the lung.MethodsBetween 1996 and December 2006, 121 patients presenting with adenocarcinomas that had a diameter ≤2 cm were analyzed. The clinicopathological records of the patients were examined for age, gender, nodal status (c-N and p-N), tumor size, serum carcinoembryonic antigen level, histologic subtype, and smoking history. A histologic subtype was defined using a modified World Health Organization classification. These subtypes are bronchioloalveolar carcinoma (BAC), adenocarcinoma with little or no BAC component (Non or min BAC), and mixed bronchioloalveolar carcinoma with other adenocarcinoma components.ResultsThe overall 5-year survival rates were 94.4% for never-smokers (N = 55) and 79.2% for smokers (N = 66) (p = 0.05). Cancer-specific 5-year survival rates were 98.0% for never-smokers and 80.4% for smokers (p = 0.03). Gender, serum carcinoembryonic antigen level, and histologic subtype were significantly associated with smoking status. Histologic subtype (Non or min BAC) was the only significant prognostic factor in multivariate analyses. The prevalence of smoking by histologic subtype was 27.3% for BAC, 43.2% for mixed bronchioloalveolar carcinoma, and 74.6% for Non or min BAC. The prevalence was significantly higher in Non or min BAC than in the others. Furthermore, the smoking index (daily cigarette consumption times years of smoking) was significantly higher in Non or min BAC than in the other two subtypes. In addition, patients with a high smoking index showed a greater percentage of Non or min BAC subtypes. Finally, male gender was associated with Non or min BAC independent of smoking status (p = 0.03).ConclusionsWhen adenocarcinomas were small (diameter ≤2 cm) cigarette smoking and male gender were associated with Non or min BAC histologic subtypes, which are thought to have more aggressive biologic features resulting in poorer outcome compared with other subtypes