Sex differences in lung cancer survival: do tumors behave differently in elderly women?

PURPOSE Women with lung cancer appear to have better survival. Whether this results from better response to treatment, different tumor biology, or a longer life expectancy is not well understood. This study sought to assess sex differences in the natural history of lung cancer after controlling for unrelated causes of death and type of treatment. METHODS This study included 18,967 elderly patients with stage I and II non-small-cell lung cancer diagnosed between 1991 and 1999 from the Surveillance, Epidemiology, and End Results registry linked to Medicare records. Patients were grouped into three categories according to the treatment received: surgery, radiation or chemotherapy but no surgery, and untreated cases. We used stratified and multivariate analyses to evaluate sex differences in survival using three methods to control for competing risks: lung cancer-specific survival, overall survival adjusting for comorbidities, and relative survival. Sensitivity analysis was used to test whether potential differences in smoking could account for the observed association of sex with survival. RESULTS Women in all treatment groups had better lung cancer-specific, overall, and relative survival than did men (P < .0001). Stratified and multivariate analyses showed that women had better survival than did men after controlling for confounders. Sensitivity analyses showed that potential sex differences in smoking did not explain our findings. CONCLUSION In this national, population-based sample, elderly women with early lung cancer had better risk-adjusted survival regardless of the type of treatment. That sex differences were observed among untreated patients suggests that lung cancer in women may have a different natural history.

[1]  R. Severson,et al.  Lung cancer in women: analysis of the national Surveillance, Epidemiology, and End Results database. , 2005, Chest.

[2]  E. van Marck,et al.  Prognostic value of smoking status in operated non-small cell lung cancer. , 2005, Lung cancer.

[3]  L. Stangeland,et al.  The female gender has a positive effect on survival independent of background life expectancy following surgical resection of primary non-small cell lung cancer: a study of absolute and relative survival over 15 years. , 2005, Lung cancer.

[4]  B. Williams,et al.  Duration of smoking abstinence as a predictor for non-small-cell lung cancer survival in women. , 2005, Lung cancer.

[5]  E. Tan,et al.  The impact of smoking status on the behavior and survival outcome of patients with advanced non-small cell lung cancer: a retrospective analysis. , 2004, Chest.

[6]  P. Kvale,et al.  Lung carcinoma symptoms—An independent predictor of survival and an important mediator of African‐American disparity in survival , 2004, Cancer.

[7]  G. Bepler,et al.  Improved survival in never-smokers vs current smokers with primary adenocarcinoma of the lung. , 2004, Chest.

[8]  Peter B Bach,et al.  Lung cancer in US women: a contemporary epidemic. , 2004, JAMA.

[9]  Paul W Dickman,et al.  Regression models for relative survival , 2004, Statistics in medicine.

[10]  M. Spitz,et al.  Hormone Replacement Therapy and Lung Cancer Risk , 2004, Clinical Cancer Research.

[11]  D. Sugarbaker,et al.  Menopausal effects on presentation, treatment, and survival of women with non-small cell lung cancer. , 2003, The Annals of thoracic surgery.

[12]  Mary W. Carter Variations in hospitalization rates among nursing home residents: the role of discretionary hospitalizations. , 2003, Health services research.

[13]  M. Brundage,et al.  Prognostic factors in non-small cell lung cancer: a decade of progress. , 2002, Chest.

[14]  Beth A Virnig,et al.  Utility of the SEER-Medicare Data to Identify Chemotherapy Use , 2002, Medical care.

[15]  A. Haugen,et al.  Expression of estrogen receptors α and β in human lung tissue and cell lines , 2002 .

[16]  G. Cooper,et al.  Use of SEER-Medicare Data for Measuring Cancer Surgery , 2002, Medical care.

[17]  K. Roszkowski,et al.  Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases. , 2002, Annals of oncology : official journal of the European Society for Medical Oncology.

[18]  J. Luketich,et al.  Human Non-Small Cell Lung Tumors and Cells Derived from Normal Lung Express Both Estrogen Receptor α and β and Show Biological Responses to Estrogen , 2002 .

[19]  W. E. Morgan,et al.  Do women live longer following lung resection for carcinoma? , 2002, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[20]  J. Gustafsson,et al.  Expression, Function, and Clinical Implications of the Estrogen Receptor β in Human Lung Cancers , 2001 .

[21]  G. Hutchins,et al.  Problems with proper completion and accuracy of the cause-of-death statement. , 2001, Archives of internal medicine.

[22]  James F. Babb,et al.  Gender differences in genetic susceptibility for lung cancer. , 2000, Lung cancer.

[23]  N. Tsubota,et al.  Lung cancer in women: sex-associated differences in survival of patients undergoing resection for lung cancer. , 2000, Chest.

[24]  J L Warren,et al.  Development of a comorbidity index using physician claims data. , 2000, Journal of clinical epidemiology.

[25]  S. Anttila,et al.  Survival in operable non‐small‐cell lung cancer: Role of p53 mutations, tobacco smoking and asbestos exposure , 2000, International journal of cancer.

[26]  C. Rochester,et al.  Smoking and chronic obstructive pulmonary disease. , 2000, Clinics in chest medicine.

[27]  E. Mark,et al.  Implications and prognostic value of K-ras mutation for early-stage lung cancer in women. , 1999, Journal of the National Cancer Institute.

[28]  D. Phillips,et al.  Sex differences in lung CYP1A1 expression and DNA adduct levels among lung cancer patients. , 1999, Cancer research.

[29]  K. Hiroshima,et al.  Smoking before surgery predicts poor long-term survival in patients with stage I non-small-cell lung carcinomas. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  C. Emond,et al.  Lung cancer in women compared with men: stage, treatment, and survival. , 1998, The Annals of thoracic surgery.

[31]  R. Kronmal,et al.  Assessing the sensitivity of regression results to unmeasured confounders in observational studies. , 1998, Biometrics.

[32]  M. Thun,et al.  Cigarette smoking and changes in the histopathology of lung cancer. , 1997, Journal of the National Cancer Institute.

[33]  C. Mountain,et al.  Revisions in the International System for Staging Lung Cancer. , 1997, Chest.

[34]  D. Phillips,et al.  p53 mutations in lung tumours: relationship to gender and lung DNA adduct levels. , 1996, Carcinogenesis.

[35]  E. Wynder,et al.  Differences in lung cancer risk between men and women: examination of the evidence. , 1996, Journal of the National Cancer Institute.

[36]  D. Phillips,et al.  Different susceptibility to smoking-induced DNA damage among male and female lung cancer patients. , 1994, Cancer research.

[37]  A. Miller,et al.  Are female smokers at higher risk for lung cancer than male smokers? A case-control analysis by histologic type. , 1993, American journal of epidemiology.

[38]  L. Kessler,et al.  Potential for Cancer Related Health Services Research Using a Linked Medicare‐Tumor Registry Database , 1993, Medical care.

[39]  R. Deyo,et al.  Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. , 1992, Journal of clinical epidemiology.

[40]  D. Sackett,et al.  The Ends of Human Life: Medical Ethics in a Liberal Polity , 1992, Annals of Internal Medicine.

[41]  J. Crowley,et al.  Determinants of improved outcome in small-cell lung cancer: an analysis of the 2,580-patient Southwest Oncology Group data base. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  M. Boyd,et al.  Expression of CYP1A1 gene in patients with lung cancer: evidence for cigarette smoke-induced gene expression in normal lung tissue and for altered gene regulation in primary pulmonary carcinomas. , 1990, Journal of the National Cancer Institute.

[43]  H. Golomb,et al.  Sex-associated differences in presentation and survival in patients with lung cancer. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[44]  S. Steinberg,et al.  Female patients with small cell lung cancer live longer than male patients. , 1988, The American journal of medicine.

[45]  Timo Hakulinen,et al.  Regression Analysis of Relative Survival Rates , 1987 .

[46]  D. Ettinger,et al.  Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study. , 1986, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  H. Burdo,et al.  The autopsy as a measure of accuracy of the death certificate. , 1985, The New England journal of medicine.

[48]  C. Percy,et al.  Accuracy of cancer death certificates and its effect on cancer mortality statistics. , 1981, American journal of public health.

[49]  J. Crowley,et al.  Covariance Analysis of Heart Transplant Survival Data , 1977 .

[50]  F. Ederer,et al.  The relative survival rate: a statistical methodology. , 1961, National Cancer Institute monograph.

[51]  E. Kaplan,et al.  Nonparametric Estimation from Incomplete Observations , 1958 .

[52]  O. Miettinen,et al.  Women's susceptibility to tobacco carcinogens. , 2004, Lung cancer.

[53]  F. Khuri,et al.  Sex differences in survival in non-small cell lung cancer patients 1974-1998. , 2004, Acta oncologica.

[54]  E. Vokes,et al.  Sex-associated differences in survival of patients undergoing resection for lung cancer. , 2000, The Annals of thoracic surgery.

[55]  M. Usel,et al.  Sex differences in presentation, management, and prognosis of patients with non-small cell lung carcinoma. , 2000, The Journal of thoracic and cardiovascular surgery.

[56]  D. Cox Regression Models and Life-Tables , 1972 .