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Never-Smokers With Lung Cancer: Epidemiologic Evidence of a Distinct Disease Entity

Chee-Keong Toh, Fei Gao, Wan-Teck Lim, Swan-Swan Leong, Kam-Weng Fong, Swee-Peng Yap, Anne A.L. Hsu, Philip Eng, Heng-Nung Koong, Agasthian Thirugnanam, Eng-Huat Tan

From the Department of Medical Oncology; Division of Clinical Trials and Epidemiological Sciences; Department of Therapeutic Radiology; Department of Surgical Oncology, National Cancer Centre; and the Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore.

Address reprint requests to Chee-Keong Toh, MD, Department of Medical Oncology, National Cancer Centre, 11 Hospital Dr, Singapore, Singapore 169610; e-mail: dmotck{at}nccs.com.sg

Purpose Tobacco smoke is a definite causative agent for lung cancer. It is increasingly being recognized that never-smokers can be afflicted with non–small-cell lung cancer (NSCLC). We aim to assess survival differences between smokers and never-smokers with NSCLC.

Patients and Methods We analyzed 975 NSCLC patients who presented from January 1999 to December 2002. Clinical characteristics among current-, former- and never-smokers were tested using ² or Kruskal-Wallis test. The hazard ratio (HR) for death and its 95% CI were calculated by Cox regression.

Results Of 975 patients, 59 had no smoking history and 33 had no quit time recorded. Of 883 patients analyzed, 286 patients (32.4%) were never-smokers. One hundred ninety-six never-smokers (68.5%) were females compared with 12% among current- and 13% among former-smokers (P < .001). There was a significant difference in histologic subtype between never-smokers and smokers: 69.9% with adenocarcinoma versus 39.9% (current-smokers) versus 47.3% (former-smokers); 5.9% with squamous cell carcinoma versus 35.7% (current-smokers) versus 28% (former-smokers; P < .001). Smokers had significantly poorer performance status (P = .002) and higher median age at diagnosis (P < .001) while more never-smokers presented with advanced disease (P = .002). Eight hundred and five patients (82.6%) died by May 30, 2005. The HR for smokers was significantly higher on both univariate and multivariate analysis (HR, 1.297; 95% CI, 1.040 to 1.619).

Conclusion Never-smokers comprised a high proportion of NSCLC patients in Singapore. Definite epidemiologic differences exist between never-smokers and smokers. Differences in survival outcome further suggest that the biology underlying the pathogenesis and behavior of the disease may be different for never-smokers.

Presented in part at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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