A critical appraisal of overdiagnosis: estimates of its magnitude and implications for lung cancer screening

Background: The magnitude of overdiagnosis is a critical and unresolved issue in lung cancer (LC) screening:(1) its contribution to the increase in survival constitutes specious evidence of benefit;(2) overdiagnosed individuals who undergo resection will experience a reduction in life expectancy, partially or completely offsetting the benefit received by others in whom earlier intervention proves curative. Method: Critical analysis of studies in opposition and support of the view that LC screening imposes a substantial burden of overdiagnosis. Results: Approximately 25%, possibly more, of radiographically (chest x ray) diagnosed LC appears to be overdiagnosed. Based on the observed tumour volume doubling time of low dose CT identified small malignant pulmonary nodules, CT will markedly augment lead time, increasing exposure to competing lethal morbidities, thereby increasing overdiagnosis. Conclusion: To reduce all-cause mortality, CT screening will need to reduce LC mortality by an amount that exceeds the increase in mortality attributable to surgery and loss of pulmonary reserve in persons who are overdiagnosed or pathologically understaged (ie, with occult micrometastases). Presently, there is no evidence that CT screening will achieve any reduction in LC mortality.

[1]  Ugo Pastorino,et al.  Computed tomography screening and lung cancer outcomes. , 2007, JAMA.

[2]  N. Anthonisen,et al.  Airways obstruction and the risk for lung cancer. , 1987, Annals of internal medicine.

[3]  David Spizarny,et al.  Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. , 2005, Lung cancer.

[4]  Anne-Marie Sykes,et al.  CT screening for lung cancer: five-year prospective experience. , 2005, Radiology.

[5]  E. Patz,et al.  Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias. , 2001, Lung cancer.

[6]  D. Sin,et al.  The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. , 2005, Chest.

[7]  Donna L. Hoyert,et al.  Vital Statistics of the United States , 1940, Nature.

[8]  D. Haggstrom,et al.  All-cause mortality in randomized trials of cancer screening. , 2002, Journal of the National Cancer Institute.

[9]  P. Bachelor.  FREQUENCY , 1973, Sorrow & Solace.

[10]  S. Sone,et al.  Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner , 2001, British Journal of Cancer.

[11]  R. Schreiber,et al.  Cancer immunoediting: from immunosurveillance to tumor escape , 2002, Nature Immunology.

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

[13]  J Polák,et al.  Lung cancer detection results of a randomized prospective study in Czechoslovakia , 1986, Cancer.

[14]  G. Byrnes,et al.  Screening for lung cancer. , 2004, The Cochrane database of systematic reviews.

[15]  S. Thibodeau,et al.  Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. , 2005, Chest.

[16]  G. Silvestri,et al.  What happens to patients undergoing lung cancer surgery? Outcomes and quality of life before and after surgery. , 2002, Chest.

[17]  Improved survival and higher mortality: the conundrum of lung cancer screening. , 2002, Chest.

[18]  J. Weinstein,et al.  Is the Gene Expression Pattern of Lung Cancer Detected by Screening With Spiral Computed Tomography Different from That of Symptom-Detected Lung Cancer? , 2004, Clinical Cancer Research.

[19]  William J Kostis,et al.  Overdiagnosis in chest radiographic screening for lung carcinoma , 2003, Cancer.

[20]  W C Black,et al.  Overdiagnosis: An underrecognized cause of confusion and harm in cancer screening. , 2000, Journal of the National Cancer Institute.

[21]  U. Pastorino,et al.  Lung Cancers Detected by Screening with Spiral Computed Tomography Have a Malignant Phenotype when Analyzed by cDNA Microarray , 2004, Clinical Cancer Research.

[22]  C. Percy,et al.  Surveillance, epidemiology, and end results : incidence and mortality data, 1973-1977 , 1981 .

[23]  E. Glatstein,et al.  CT Screening for Lung Cancer: Five-Year Prospective Experience , 2006 .

[24]  D. Geddes,et al.  The natural history of lung cancer: a review based on rates of tumour growth. , 1979, British journal of diseases of the chest.

[25]  James L Mulshine,et al.  Lung cancer screening. , 2005, The oncologist.

[26]  K P Offord,et al.  Higher risk of lung cancer in chronic obstructive pulmonary disease. A prospective, matched, controlled study. , 1986, Annals of internal medicine.

[27]  K. Nakata,et al.  Surgically curable peripheral lung carcinoma: correlation of thin-section CT findings with histologic prognostic factors and survival. , 2005, Chest.

[28]  O S Miettinen,et al.  CT screening for lung cancer: coping with nihilistic recommendations. , 2001, Radiology.

[29]  S. Friberg,et al.  On the growth rates of human malignant tumors: Implications for medical decision making , 1997, Journal of surgical oncology.

[30]  T. Naruke,et al.  Survival for clinical stage I lung cancer not surgically treated. Comparison between screen‐detected and symptom‐detected cases , 1992, Cancer.

[31]  M. L. R. D. Christenson.  Computed Tomography Screening and Lung Cancer Outcomes , 2008 .

[32]  J. Reich.  Assessing the efficacy of lung cancer screening. , 2006, Radiology.

[33]  P C Prorok,et al.  Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. , 2000, Journal of the National Cancer Institute.

[34]  Douglas C McCrory,et al.  Screening for lung cancer: a review of the current literature. , 2003, Chest.

[35]  M. Melamed,et al.  The effect of surgical treatment on survival from early lung cancer. Implications for screening. , 1992, Chest.

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

[37]  T L Petty,et al.  Screening strategies for early detection of lung cancer: the time is now. , 2000, JAMA.

[38]  S Sone,et al.  Growth rate of small lung cancers detected on mass CT screening. , 2000, The British journal of radiology.

[39]  N. Anthonisen.  Smoking, lung function, and mortality , 2000, Thorax.

[40]  D. M. Parkin,et al.  Lack of benefit from semi‐annual screening for cancer of the lung: Follow‐up report of a randomized controlled trial on a population of high‐risk males in czechoslovakia , 1990, International journal of cancer.

[41]  Edward F Patz,et al.  Estimate of lung cancer mortality from low-dose spiral computed tomography screening trials: implications for current mass screening recommendations. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  Peter B Bach,et al.  Screening for lung cancer: the guidelines. , 2003, Chest.

[43]  R. Chiba,et al.  Atypical adenomatous hyperplasia of the lung and its differentiation from adenocarcinoma. Characterization of atypical cells by morphometry and multivariate cluster analysis , 1993, Cancer.

[44]  O S Miettinen,et al.  Early Lung Cancer Action Project , 2001, Cancer.

[45]  E. Bergstralh,et al.  Screening for lung cancer. A critique of the mayo lung project , 1991, Cancer.

[46]  G. Byrnes,et al.  Incidental lung cancers identified at coronial autopsy: implications for overdiagnosis of lung cancer by screening. , 2005, Respiratory medicine.

[47]  H. Kawabata,et al.  Early Lung Cancer Action Project , 1999, The Lancet.

[48]  B. Szende,et al.  Misdiagnosis of lung cancer in a 2000 consecutive autopsy study in Budapest. , 1996, General & diagnostic pathology.

[49]  G. Swanson,et al.  Surveillance, epidemiology, and end results: incidence and mortality data, 1973-77. , 1981, National Cancer Institute monograph.

[50]  A. Feinstein,et al.  Incidence, prevalence, and evidence. Scientific problems in epidemiologic statistics for the occurrence of cancer. , 1987, The American journal of medicine.

[51]  D. Eddy,et al.  Screening for lung cancer. , 1989, Annals of internal medicine.

[52]  H Nakata,et al.  Evolution of peripheral lung adenocarcinomas: CT findings correlated with histology and tumor doubling time. , 2000, AJR. American journal of roentgenology.

[53]  C. Wells,et al.  The 'epidemiologic necropsy'. Unexpected detections, demographic selections, and changing rates of lung cancer. , 1987, JAMA.

[54]  O. Miettinen,et al.  Early Lung Cancer Action Project: overall design and findings from baseline screening , 1999, The Lancet.

[55]  P. Zatloukal,et al.  Czech Study on Lung Cancer Screening: post-trial follow-up of lung cancer deaths up to year 15 since enrollment. , 2000 .

[56]  C. Wells,et al.  More lung cancer but better survival. Implications of secular trends in "necropsy surprise" rates. , 1989, Chest.

[57]  Michael C. Minnotte,et al.  Noncancer deaths in white adult cancer patients. , 1993, Journal of the National Cancer Institute.

[58]  D. Schottenfeld,et al.  The autopsy as a measure of accuracy of the death certificate. , 1982, Bulletin of the New York Academy of Medicine.

[59]  O. Miettinen,et al.  Small stage I cancers of the lung: genuineness and curability. , 2003, Lung cancer.

[60]  John Quackenbush.  Microarray analysis and tumor classification. , 2006, The New England journal of medicine.

[61]  W F Taylor,et al.  Lung cancer screening: the Mayo program. , 1986, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[62]  D. Parkin,et al.  Czech study on lung cancer screening , 2000, Cancer.