Differences in Epidemiology, Histology, and Survival Between Cigarette Smokers and Never-Smokers Who Develop Non-small Cell Lung Cancer

Ayesha Bryant, MSPH, MD; Robert James Cerfolio, MD, FCCP


CHEST. 2007;132(1):185-192. 

In This Article

Abstract and Introduction

Background: The impact that smoking cigarettes has on the characteristics and survival of patients with non-small cell lung cancer (NSCLC) is disputed.
Methods: A retrospective cohort study using a prospective database of patients with NSCLC over a 6-year period. Clinical and histologic characteristics and survival rates were compared between smokers and never-smokers.
Results: There were 730 patients; 562 patients (77%) were smokers and 168 patients (23%) were never-smokers. The overall 5-year survival rate was greater in never-smokers (64%) compared to smokers (56%; p = 0.031). Never-smokers were more likely to be younger (p = 0.04), female (p = 0.01), symptomatic at the time of presentation (p < 0.001), have poorly differentiated tumors (p = 0.04), and have a higher maximum standardized uptake value (maxSUV) on positron emission tomography (PET) (p = 0.026) than smokers. The stage-specific 5-year survival rate was greater for never-smokers compared to smokers for stage I disease (62% vs 75%, respectively; p = 0.02), stage II disease (46% vs 53%, respectively; p = 0.09), and stage III disease (36% vs 41%, respectively; p = 0.13). The 5-year survival rate was significantly lower in patients who had a smoking history of > 20 pack-years.
Conclusions: Never-smokers in whom NSCLC develops are more likely to be young, female, and have poorly differentiated tumors with higher maxSUV values on PET scans. Never-smokers with early-stage cancer have a significantly better survival rate than smokers. Patients with a smoking history of ≥ 20 pack-years have worse survival. Thus, smoking not only causes lung cancer, but once NSCLC is diagnosed, the prognosis becomes worse. A biological, hormonal, and genetic explanation is currently lacking to explain these findings, and these data may help to improve treatment and surveillance.

Lung cancer is responsible for more deaths than the next three most common solid organ cancers combined in both men and women. In 2006, there were estimated to be 174,470 new patients in whom lung cancer was diagnosed in the United States and 162,460 deaths attributed to it.[1] In fact, even after 3 decades of improvements in staging and therapy, the 5-year mortality rate for all patients with lung cancer remains at an extraordinarily high rate of 85%.[2] Despite evidence that smoking cigarettes causes lung cancer, the effect that smoking status has on survival after diagnosis is controversial. For example, several studies[3,4,5,6,7,8] have reported that smoking cigarettes is a negative prognostic factor, whereas other reports[9,10,11,12] have found no association between lung cancer and smoking cigarettes. This controversy is enhanced by the limited availability of data. For example, even large national registries, such as the Survival, Epidemiology and End Results database do not contain information on smoking status for patients with non-small cell lung cancer (NSCLC).

It has been estimated that 10% of men and 20% of women in whom lung cancer develops are never-smokers. The fact that lung cancer afflicts lifelong never-smokers has recently received national attention with the death of actress Dana Reeve. The purpose of this study was to examine the differences in the epidemiology and histologic distribution of NSCLC in smokers with NSCLC compared to never-smokers with NSCLC. We also wanted to assess the survival difference between smokers and nonsmokers who were carefully staged and then underwent similar treatment strategies based on the stage of their disease.