Screening for Lung Cancer

Summary Type: Screening
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about tests used to detect or screen for lung cancer.

Screening for Lung Cancer

Summary of Evidence

Separate PDQ summaries on Prevention of Lung Cancer, Small Cell Lung Cancer Treatment, Non-Small Cell Lung Cancer Treatment, and Levels of Evidence for Cancer Screening and Prevention Studies are also available.

Screening for Lung Cancer with Chest X-Ray and/or Sputum Cytology

Benefits

Based on fair evidence, screening does not reduce mortality from lung cancer.

Description of the Evidence
• Study Design : Evidence obtained from randomized controlled trials.
• Internal Validity : Fair, due to lack of unscreened groups and contamination.
• Consistency : Good.
• Direction and Magnitude of Effect : No evidence of effect.
• External Validity : Fair, due to lack of women and minority groups.

Harms

Based on solid evidence, screening would lead to false-positive tests and unnecessary invasive diagnostic procedures and treatments.

Description of the Evidence
• Study Design : Evidence obtained from randomized controlled trials.
• Internal Validity : Fair.
• Consistency : Good.
• Direction and Magnitude of Effect : False-positive results range from 4% to 15%; there is a possibility of overdiagnosis and overtreatment (magnitude uncertain).
• External Validity : Fair.

Screening for Lung Cancer with Low-Dose Helical Computed Tomography (LDCT)

Benefits

The evidence is inadequate to determine whether screening reduces mortality from lung cancer.

Description of the Evidence
• Study Design : Evidence obtained from cohort or case-control studies.
• Internal Validity : Poor for answering the question of mortality reduction from screening with LDCT.
• Consistency : Good.
• Direction and Magnitude of Effect : Cannot determine from the available studies.
• External Validity : Not applicable, as the internal validity of the evidence is poor.

Harms

Based on solid evidence, screening would lead to false-positive tests and unnecessary invasive diagnostic procedures and treatments.

Description of the Evidence
• Study Design : Evidence obtained from cohort or case-control studies.
• Internal Validity : Poor.
• Consistency : Good.
• Direction and Magnitude of Effect : False-positive results range from 20% to 50%; overdiagnosis and overtreatment are possible (magnitude uncertain).
• External Validity : Fair.

Significance

Incidence and Mortality

Lung cancer is the second most commonly occurring noncutaneous cancer in the United States and is the leading cause of cancer deaths. In 2007 alone, it is estimated that there will be 213,380 new cases diagnosed, and 70,880 women and 89,510 men will die due to this disease.¹ The lung cancer death rate rose rapidly over several decades in both sexes, with a persistent decline for males commencing in 1991.^1,

Tobacco Use and Secondhand Smoke

The most important risk factor for lung cancer (as well as for many other cancers) is tobacco use.^2,3 Cigarette smoking has been definitively established by epidemiologic and preclinical animal experimental data as the primary cause of lung cancer. This causative link has been widely recognized since the 1960s, when national reports in Great Britain and the United States brought the cancer risk of smoking prominently to the public’s attention.³ The percentages of lung cancers estimated to be caused by tobacco smoking in males and females are 90% and 78%, respectively.

Environmental or secondhand tobacco smoke is also implicated in causing lung cancer.⁴ Environmental tobacco smoke has the same components as inhaled mainstream smoke, although in lower absolute concentrations; between 1% and 10% depending on the constituent. Carcinogenic compounds in tobacco smoke include the polynuclear aromatic hydrocarbons (PAHs), including the classical carcinogen benzo[a]pyrene (BaP) and the nicotine-derived tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In rodents, total doses of both PAH and NNK that are similar to doses received by humans in a lifetime of smoking induce pulmonary tumors.⁵ Elevated biomarkers of tobacco exposure, including urinary cotinine, tobacco-related carcinogen metabolites, and carcinogen-protein adducts, are seen in passive or secondhand smokers.^6,7,8,9,10,

Lung cancer is considered to be the endstage of multistep carcinogenesis. Suggestive evidence of genetic damage is the association of cigarette smoking with the formation of the deoxyribonucleic acid adducts in human lung tissue. An unequivocal link between tobacco smoke and lung carcinogenesis has been established by molecular data.^11,12,

Many other exposures have been established as causally associated with lung cancer, but even the combined effect of these additional factors is very small compared to cigarette smoking.¹³ These additional causal factors are primarily related to occupational exposures to agents such as asbestos, arsenic, chromium, nickel, and radon.¹³ Radon, a naturally occurring gas, is of relevance to the general public because of the potential exposure in homes.^13,

¹ American Cancer Society.: Cancer Facts and Figures 2007. Atlanta, Ga: American Cancer Society, 2007. Also available online. Last accessed March 5, 2007.

² U.S. Department of Health and Human Services.: The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, Ga: U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health. Available online. Last accessed February 16, 2007.

³ Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. Washington, DC: US Department of Health, Education, and Welfare, 1965. PHS Publ No 1103.

⁴ Hackshaw AK, Law MR, Wald NJ: The accumulated evidence on lung cancer and environmental tobacco smoke. BMJ 315 (7114): 980-8, 1997.

⁵ Cinciripini PM, Hecht SS, Henningfield JE, et al.: Tobacco addiction: implications for treatment and cancer prevention. J Natl Cancer Inst 89 (24): 1852-67, 1997.

⁶ Hecht SS, Carmella SG, Murphy SE, et al.: A tobacco-specific lung carcinogen in the urine of men exposed to cigarette smoke. N Engl J Med 329 (21): 1543-6, 1993.

⁷ Finette BA, O'Neill JP, Vacek PM, et al.: Gene mutations with characteristic deletions in cord blood T lymphocytes associated with passive maternal exposure to tobacco smoke. Nat Med 4 (10): 1144-51, 1998.

⁸ Parsons WD, Carmella SG, Akerkar S, et al.: A metabolite of the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the urine of hospital workers exposed to environmental tobacco smoke. Cancer Epidemiol Biomarkers Prev 7 (3): 257-60, 1998.

⁹ Anderson KE, Carmella SG, Ye M, et al.: Metabolites of a tobacco-specific lung carcinogen in nonsmoking women exposed to environmental tobacco smoke. J Natl Cancer Inst 93 (5): 378-81, 2001.

¹⁰ Hecht SS: Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer. Carcinogenesis 23 (6): 907-22, 2002.

¹¹ Mao L, Lee JS, Kurie JM, et al.: Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 89 (12): 857-62, 1997.

¹² Wistuba II, Lam S, Behrens C, et al.: Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 89 (18): 1366-73, 1997.

¹³ Alberg AJ, Samet JM: Epidemiology of lung cancer. Chest 123 (1 Suppl): 21S-49S, 2003.

Evidence of Benefit

Chest X-Ray and Sputum Cytology

The most common screening tests for lung cancer are the chest x-ray and sputum cytology. Early studies evaluating these modalities were the:

1. Philadelphia Pulmonary Neoplasm Research Project,¹ a nonrandomized, uncontrolled study begun in 1951;
2. Veterans Administration study,² a nonrandomized, uncontrolled study performed from 1958 to 1961;
3. South London Lung Cancer Study,³ a nonrandomized, uncontrolled study done from 1955 to 1963;
4. North London Cancer Study,^4,5 a randomized study done in the early 1960s with industrial firms randomized between screening and no screening; and
5. Kaiser Foundation Health Plan multiphasic screening trial,^6,7 a controlled trial begun in 1964 with annual chest x-ray, spirometry, and medical questionnaire as part of the multiphasic screening.

None of these studies reported a statistically significant benefit of screening on lung cancer mortality. As an example, the South London study reported an increase in survival from the time of diagnosis of screen-detected lung cancer cases compared with other cases found in the same geographical region. There was, however, no adjustment for self-selection bias, lead-time bias, overdiagnosis bias, or length bias. Additionally, these studies were small, with a short follow-up period of typically less than 10 years, so that a small-to-moderate size or long-term effect was not demonstrable.

Other lung cancer screening investigations include a randomized trial in Czechoslovakia,⁸ a nonrandomized but controlled trial in the former German Democratic Republic (GDR),⁹ and case-control studies in the former GDR ^10, and Japan.^11,12 The participants in the randomized arms of the Czechoslovakian study were screened with x-ray and cytology at 2 different frequencies, semiannual versus every 3 years. There was no unscreened control group. No difference in lung cancer mortality was observed; the relative risk (screen group/control group) was 1.36 (95% confidence interval [CI], 0.94-1.98). The GDR nonrandomized study used semiannual chest fluoroscopy over a 6-year period in the intervention arm, while control subjects were scheduled to undergo the same exam at 1-year to 2-year intervals. Allocation was based on district of residence. No reduction was observed in lung cancer mortality; the relative risk (screen group/control group) was 1.34 (95% CI, 0.94-1.98). Chest x-rays originally used for control of tuberculosis were evaluated in the German case-control study. The odds ratio (OR) showed no association between lung cancer death and having received a screening chest x-ray in both a general population-based control group (OR 0.9; 95% CI, 0.5-1.5) and a hospital-based control group (OR 1.1; 95% CI, 0.7-1.8).¹⁰ X-ray histories among deceased lung cancer cases and matched controls were considered in a Japanese case-control study. In contrast to the German study, there was a suggestion of some screening benefit; the odds ratio of dying from lung cancer for those screened within 12 months versus those not screened was 0.72 (95% CI, 0.50-1.03).¹¹ A meta-analysis of 4 other case-control studies conducted in Japan suggested mortality reductions of approximately 40%,¹³ but potential for bias in these studies has been noted.^11,

Three other randomized trials have been conducted. The Mayo Lung Project (MLP) was initiated in 1971, and involved males 45 years or older who were heavy smokers.^14,15,16 Subjects free of lung cancer on initial screening were randomized either to be offered screening with sputum cytology and chest x-ray every 4 months or to a group merely advised once at baseline to seek screening annually. At Johns Hopkins University ^17,18,19,20 and Memorial Sloan-Kettering Cancer Center,^21,22 individuals were randomized to intervention and control groups, which were both offered annual chest x-ray. In addition, the intervention group was offered sputum cytology every 4 months. None of the 3 trials reported a reduction in lung cancer mortality in the more intensively screened study group compared with the control group. Extension of follow-up to a median of 20.5 years in the MLP did not alter this conclusion.²³ The sustained excess of incident cases of lung cancer in the screened versus unscreened arms of the MLP during long-term follow-up, in the absence of evidence of a reduction in mortality, suggests that chest x-rays resulted in overdiagnosis of lung cancer.²⁴

The Mayo trial is the most pertinent to assessing annual x-ray screening because the use of screening x-rays differed in the 2 arms. There are several reservations about the Mayo study. The study was designed to detect a 50% reduction in lung cancer mortality and had insufficient power to demonstrate a lesser but medically important reduction of 10% to 15%. Also, about 50% of men in the control group received an annual chest x-ray,¹⁶ so that contamination may have been sufficient to obscure an effect. Therapeutic advances may render early detection more effective today. Additionally, the spectrum of lung cancer type has shifted over the last 2 decades. Whereas the most common type used to be squamous cell cancer (usually centrally located), the most common type is now adenocarcinoma (usually peripherally located). The latter may be more amenable to early detection by chest x-ray. In contrast, sputum cytology is more sensitive in the detection of squamous cell cancer than in detecting adenocarcinoma.^25,26,

In summary, there is no good evidence that screening for lung cancer using chest x-ray or sputum cytology can reduce lung cancer mortality. Sputum cytology has not been shown to be effective when used as an adjunct to annual chest x-ray. Screening with chest x-ray plus sputum cytology appears to detect lung cancer at an earlier stage, but this would be expected in a screening test whether or not it was effective at reducing mortality. Similarly, case survival was improved relative to cases diagnosed through usual care, but this may simply reflect lead-time bias or overdiagnosis bias.²⁷ No reduction in lung cancer mortality has been observed.

Uncertainty in interpretation of results from completed studies has led to conflicting positions in the medical community and confusion in populations at risk regarding the value of chest x-ray screening. Only a properly designed randomized trial can demonstrate whether an important benefit exists. To this end, the National Cancer Institute (NCI) is conducting the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. This is a long-term randomized controlled trial in which 37,000 men are screened for prostate, lung, and colorectal cancers and 37,000 women are screened for lung, colorectal, and ovarian cancers. The lung component uses annual posteroanterior (PA) view chest x-ray as the screening modality. Equal numbers of men and women are followed with routine medical care as controls.^28, In the baseline screen, 9% of participants had a positive screen, with significant increases in prevalence of positive screens with older age and more extensive smoking histories.²⁹ A total of 126 participants were subsequently diagnosed with lung cancer, and approximately one half of these were stage I.^29,

Spiral Computed Tomography (CT)

There are intensive efforts to improve lung cancer screening with newer technologies, including low-dose helical computed tomography (LDCT) and molecular techniques.^30,31 LDCT is more sensitive than chest radiography. In the Early Lung Cancer Action Project (ELCAP) screening study,³¹ LDCT detected almost 6 times as many stage I lung cancers as chest radiography and most of these tumors were no larger than 1 cm in diameter. The effectiveness of screening with LDCT has not yet been evaluated in a controlled clinical trial, however.

Eight ongoing observational studies of LDCT in various parts of the world have been reported and summarized.³² These are relatively small studies, ranging from about 600 to 8,000 participants, begun between 1992 and 2000. Most include a substantial percentage of females, and the studies in Japan include never smokers. Findings include a nodule or positivity rate of 5% to 51%, 0.4% to 3% lung cancers, 50% to 95% adenocarcinomas, 50% to 91% stage I or IA cancers, and estimates of sensitivity ranging from 40% to 95%.

Two harms must be considered against any potential benefit of screening with LDCT: false-positive test results and overdiagnosis. The false-positive test result, which is the more common and familiar harm, may lead to anxiety and invasive diagnostic procedures, such as percutaneous needle biopsy or thoracotomy. In the Early Lung Cancer Action Project (ELCAP),³¹ which used a CT slice thickness of 10 mm, noncalcified nodules were detected in 21% of subjects without lung cancer at the prevalence screen. Thirty-one of 233 (13%) individuals with noncalcified nodules underwent biopsies, of which close to 90% (27/31) resulted in a diagnosis of malignancy, and the prevalence of cancers detected was 2.7%. A study in Ireland,³³ which aimed to reproduce the ELCAP study in high-risk, but younger, individuals revealed a similar proportion of noncalcified nodules were detected using 10 mm CT slice thickness. In the Irish study (N = 449), however, the prevalence of cancers detected was substantially smaller (0.46%). Furthermore, several individuals underwent invasive procedures for ultimately benign conditions (3 of 4 patients with nodules >10 mm who underwent biopsy had benign cytology; one had a thoracotomy that confirmed benign disease; 3 patients with mediastinal masses underwent biopsy and 2 had benign cysts). In 2 other studies, which used 5 mm CT slices, noncalcified nodules were detected in a much higher proportion of subjects.^34,35 In the Mayo Clinic study,³⁴ noncalcified nodules were detected in 51% of 1,520 subjects at the prevalence screen and cumulatively in 74% after 5 subsequent annual screens.³⁶ Ninety-five percent of these nodules were less than 8 mm in diameter, for which the recommended follow-up was noncontrast CT in 3 to 6 months. However, 8 subjects had surgery for benign lesions, 5 of which appeared to grow on follow-up CT. In addition, screening with LDCT can detect abnormalities other than noncalcified nodules, including enlarged lymph nodes, abdominal aortic aneurysms, and renal and adrenal masses. During the first 3 rounds of screening in the Mayo clinic study, 696 such abnormalities were found in the 1,520 subjects. It is not clear whether the detection of these abnormalities produces a net benefit.^34,

A less familiar harm is overdiagnosis,²⁷ the diagnosis of a condition that would not have become clinically significant had it not been detected by screening. In the case of screening with LDCT, overdiagnosis could lead to unnecessary diagnosis of lung cancer requiring some combination of surgery, e.g., lobectomy, chemotherapy, and radiation therapy. Although overdiagnosis is almost impossible to document in a living individual, autopsy studies suggest that many individuals die with lung cancer rather than from it. In one study, about one sixth of all lung cancers found at autopsy had not been clinically recognized before death.³⁷ Even this may be an underestimate because autopsy probably fails to detect many small lung cancers that are detectable by CT.³⁸ Studies in Japan provide additional evidence that screening with LDCT could lead to a substantial amount of overdiagnosis.³⁹ In a study in which smokers and nonsmokers were annually screened for lung cancer between 1996 to 1998 using LDCT, the overall rate of screen-detected lung cancers was very similar in the 2 groups: 0.46% for smokers (mainly men) and 0.41% for nonsmokers (mainly women).⁴⁰ The nonsmoking group may have included individuals who were at an elevated risk for lung cancers for other reasons, but no information is provided on this point. A second study involving both smokers and nonsmokers reported a similar finding of a 1.1% lung cancer detection rate in both groups.⁴¹ Confirmative studies are needed to establish the level of overdiagnosis that might be associated with CT screening for lung cancer. In that same population, the volume-doubling times of 61 lung cancers were estimated using an exponential model and successive CT images. Lesions were classified into 3 types: type G (ground glass opacity), type GS (focal glass opacity with a solid central component), and type S (solid nodule). The mean-doubling times were 813 days, 457 days, and 149 days for types G, GS, and S, respectively. In this study, annual CT screening identified a large number of slowly growing adenocarcinomas that were not visible on chest x-ray.⁴² Before spiral CT is accepted into medical practice, it is critical to determine whether this modality does more good than harm in a randomized controlled trial with lung cancer mortality as the endpoint.^43,44,

To assess the feasibility of conducting a randomized controlled trial in asymptomatic individuals at high risk of lung cancer because of a history of smoking, the NCI conducted the Lung Screening Study (LSS). Six PLCO contract screening centers recruited 3,318 heavy or long-term smokers (inclusion required a 30 pack-year smoking history) who were not participants in the PLCO trial and randomized them to receive LDCT (1,660) or chest x-ray (1,658) between September 5, 2000 and November 15, 2000. Ninety-six percent of subjects in the LDCT arm and 93% of subjects in the chest x-ray arm were screened. Findings that were suspicious for lung cancer were reported in 20.5% (325/1,586) of screened subjects in the LDCT and 9.8% of screened subjects (152/1,550) in the chest x-ray arm. After a positive screen, lung cancer was diagnosed in 1.9% (30) of screened subjects in the LDCT arm and 0.45% (7) in the chest x-ray arm. In this prevalence screen, 16 of 30 in the LDCT arm and 6 of 7 in the chest x-ray arm, were stage I. The 2 study arms were essentially identical on age, sex, and history of smoking. Men represented 60% of participants and about 60% of participants were current smokers. Positive rates were higher among current smokers and older subjects. Almost all subjects with positive screening results received at least 1 follow-up diagnostic procedure (98% in the LDCT arm and 96% in the chest x-ray arm). In a survey of all study subjects, which had greater than a 98% response rate, 2.6% of chest x-ray subjects reported having a CT exam outside the trial between annual screens and 13% of LDCT subjects had outside chest x-rays.⁴⁵ The findings at the 1-year screen and the final results of the LSS have been reported. Compliance with screening declined from 96% at baseline to 86% at 1 year in the LDCT arm and from 93% at baseline to 80% at 1 year in the chest x-ray arm. Positivity rates for the 1-year screen were 25.8% for LDCT and 8.7 % for chest x-ray. Cancer yield at 1 year for LDCT was 0.57% and 0.68% at 1 year for chest x-ray. Forty cancers in the LDCT arm (48% were stage I) and 20 in the chest x-ray arm (40% were stage I) were diagnosed over the study period. A total of 16 stage III to stage IV cancers were observed in the LDCT arm versus 9 in the chest x-ray arm.⁴⁶ This information proved the feasibility of the National Lung Screening Trial (NLST).^45,46,

The NCI is conducting the NLST, a randomized controlled trial designed to determine whether annual screening with LDCT can reduce lung cancer mortality among persons at elevated risk for that disease (NCI-NLST). More than 50,000 persons aged 55 to 74 years with a history of heavy or long-term smoking have been enrolled in NLST, and the trial is now closed to further recruitment. Participants in NLST have been randomly assigned to receive either 3 annual LDCTs or 3 annual chest x-rays. Data collection and analysis in NLST are scheduled to continue for 8 years (NLST).

¹ Boucot KR, Weiss W: Is curable lung cancer detected by semiannual screening? JAMA 224 (10): 1361-5, 1973.

² An evaluation of radiologic and cytologic screening for the early detection of lung cancer: a cooperative pilot study of the American Cancer Society and the Veterans Administration. Cancer Res 26 (10): 2083-121, 1966.

³ Nash FA, Morgan JM, Tomkins JG: South London Lung Cancer Study. Br Med J 2 (607): 715-21, 1968.

⁴ Brett GZ: The value of lung cancer detection by six-monthly chest radiographs. Thorax 23 (4): 414-20, 1968.

⁵ Brett GZ: Earlier diagnosis and survival in lung cancer. Br Med J 4 (678): 260-2, 1969.

⁶ Dales LG, Friedman GD, Collen MF: Evaluating periodic multiphasic health checkups: a controlled trial. J Chronic Dis 32 (5): 385-404, 1979.

⁷ Friedman GD, Collen MF, Fireman BH: Multiphasic Health Checkup Evaluation: a 16-year follow-up. J Chronic Dis 39 (6): 453-63, 1986.

⁸ Kubik A, Parkin DM, Khlat M, 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. Int J Cancer 45 (1): 26-33, 1990.

⁹ Wilde J: A 10 year follow-up of semi-annual screening for early detection of lung cancer in the Erfurt County, GDR. Eur Respir J 2 (7): 656-62, 1989.

¹⁰ Ebeling K, Nischan P: Screening for lung cancer--results from a case-control study. Int J Cancer 40 (2): 141-4, 1987.

¹¹ Marcus PM: Conflicting evidence in lung cancer screening: randomized controlled trials versus case-control studies. Lung Cancer 41 (1): 37-9, 2003.

¹² Sobue T, Suzuki T, Naruke T: A case-control study for evaluating lung-cancer screening in Japan. Japanese Lung-Cancer-Screening Research Group. Int J Cancer 50 (2): 230-7, 1992.

¹³ Sagawa M, Nakayama T, Tsukada H, et al.: The efficacy of lung cancer screening conducted in 1990s: four case-control studies in Japan. Lung Cancer 41 (1): 29-36, 2003.

¹⁴ Fontana RS: Early detection of lung cancer: the Mayo Lung Project. In: Prorok PC, Miller AB, eds.: Screening for Cancer, I: General Principles on Evaluation of Screening for Cancer and Screening for Lung, Bladder, and Oral Cancer. Vol. 78, Geneva, Switzerland: International Union Against Cancer, 1984, pp 107-122.

¹⁵ Fontana RS: Screening for lung cancer. In: Miller AB, ed.: Screening for Cancer. New York, NY: Academic Press, 1985, pp 377-395.

¹⁶ Fontana RS: Screening for lung cancer: recent experience in the United States. In: Hansen HH, ed.: Lung Cancer: Basic and Clinical Aspects. Boston, Ma: Martinus Nijhoff Publishers, 1986, pp 91-111.

¹⁷ Levin ML, Tockman MS, Frost JK, et al.: Lung cancer mortality in males screened by chest X-ray and cytologic sputum examination: a preliminary report. Recent Results Cancer Res 82: 138-46, 1982.

¹⁸ Stitik FP, Tockman MS: Radiographic screening in the early detection of lung cancer. Radiol Clin North Am 16 (3): 347-66, 1978.

¹⁹ Stitik FP, Tockman MS, Khouri NF: Chest radiology. In: Miller AB, ed.: Screening for Cancer. New York, NY: Academic Press, 1985, pp 163-191.

²⁰ Tockman MS, Levin ML, Frost JK, et al.: Screening and detection of lung cancer. In: Aisner J, ed.: Lung Cancer. New York, NY: Churchill Livingstone, 1985, pp 25-40.

²¹ Melamed MR, Flehinger BJ, Zaman MB, et al.: Detection of true pathologic stage I lung cancer in a screening program and the effect on survival. Cancer 47 (5 Suppl): 1182-7, 1981.

²² Melamed MR, Flehinger BJ, Zaman MB, et al.: Screening for early lung cancer. Results of the Memorial Sloan-Kettering study in New York. Chest 86 (1): 44-53, 1984.

²³ Marcus PM, Bergstralh EJ, Fagerstrom RM, et al.: Lung cancer mortality in the Mayo Lung Project: impact of extended follow-up. J Natl Cancer Inst 92 (16): 1308-16, 2000.

²⁴ Marcus PM, Bergstralh EJ, Zweig MH, et al.: Extended lung cancer incidence follow-up in the Mayo Lung Project and overdiagnosis. J Natl Cancer Inst 98 (11): 748-56, 2006.

²⁵ Thun MJ, Lally CA, Flannery JT, et al.: Cigarette smoking and changes in the histopathology of lung cancer. J Natl Cancer Inst 89 (21): 1580-6, 1997.

²⁶ Gazdar AF, Minna JD: Cigarettes, sex, and lung adenocarcinoma. J Natl Cancer Inst 89 (21): 1563-5, 1997.

²⁷ Black WC: Overdiagnosis: An underrecognized cause of confusion and harm in cancer screening. J Natl Cancer Inst 92 (16): 1280-2, 2000.

²⁸ Gohagan JK, Prorok PC, Kramer BS, et al.: The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial of the National Cancer Institute. Cancer 75(Suppl 7): 1869-1873, 1995.

²⁹ Oken MM, Marcus PM, Hu P, et al.: Baseline chest radiograph for lung cancer detection in the randomized Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. J Natl Cancer Inst 97 (24): 1832-9, 2005.

³⁰ Ahrendt SA, Chow JT, Xu LH, et al.: Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. J Natl Cancer Inst 91 (4): 332-9, 1999.

³¹ Henschke CI, McCauley DI, Yankelevitz DF, et al.: Early Lung Cancer Action Project: overall design and findings from baseline screening. Lancet 354 (9173): 99-105, 1999.

³² Manser RL, Irving LB, de Campo MP, et al.: Overview of observational studies of low-dose helical computed tomography screening for lung cancer. Respirology 10 (1): 97-104, 2005.

³³ MacRedmond R, Logan PM, Lee M, et al.: Screening for lung cancer using low dose CT scanning. Thorax 59 (3): 237-41, 2004.

³⁴ Swensen SJ, Jett JR, Hartman TE, et al.: Lung cancer screening with CT: Mayo Clinic experience. Radiology 226 (3): 756-61, 2003.

³⁵ Diederich S, Wormanns D, Semik M, et al.: Screening for early lung cancer with low-dose spiral CT: prevalence in 817 asymptomatic smokers. Radiology 222 (3): 773-81, 2002.

³⁶ Swensen SJ, Jett JR, Hartman TE, et al.: CT screening for lung cancer: five-year prospective experience. Radiology 235 (1): 259-65, 2005.

³⁷ Chan CK, Wells CK, McFarlane MJ, et al.: More lung cancer but better survival. Implications of secular trends in "necropsy surprise" rates. Chest 96 (2): 291-6, 1989.

³⁸ Dammas S, Patz EF Jr, Goodman PC: Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias. Lung Cancer 33 (1): 11-6, 2001.

³⁹ Marcus PM, Fagerstrom RM, Prorok PC, et al.: Screening for lung cancer with helical CT scanning. Clinical Pulmonary Medicine 9 (6): 323-9, 2002.

⁴⁰ Sone S, Li F, Yang ZG, et al.: Results of three-year mass screening programme for lung cancer using mobile low-dose spiral computed tomography scanner. Br J Cancer 84 (1): 25-32, 2001.

⁴¹ Li F, Sone S, Abe H, et al.: Low-dose computed tomography screening for lung cancer in a general population: characteristics of cancer in non-smokers versus smokers. Acad Radiol 10 (9): 1013-20, 2003.

⁴² Hasegawa M, Sone S, Takashima S, et al.: Growth rate of small lung cancers detected on mass CT screening. Br J Radiol 73 (876): 1252-9, 2000.

⁴³ Patz EF Jr, Goodman PC, Bepler G: Screening for lung cancer. N Engl J Med 343 (22): 1627-33, 2000.

⁴⁴ Swensen SJ: CT screening for lung cancer. AJR Am J Roentgenol 179 (4): 833-6, 2002.

⁴⁵ Gohagan J, Marcus P, Fagerstrom R, et al.: Baseline findings of a randomized feasibility trial of lung cancer screening with spiral CT scan vs chest radiograph: the Lung Screening Study of the National Cancer Institute. Chest 126 (1): 114-21, 2004.

⁴⁶ Gohagan JK, Marcus PM, Fagerstrom RM, et al.: Final results of the Lung Screening Study, a randomized feasibility study of spiral CT versus chest X-ray screening for lung cancer. Lung Cancer 47 (1): 9-15, 2005.

Changes To This Summary (02/20/2007)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Significance

Updated incidence and mortality estimates for 2007 (cited American Cancer Society as reference 1).

Questions or Comments About This Summary

If you have questions or comments about this summary, please send them to Cancer.gov through the Web site’s Contact Form. We can respond only to email messages written in English.

More Information

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database.
  • Full description of the NCI PDQ database.

Additional PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment
  • Treatment options for adult cancers.
• PDQ® Cancer Information Summaries: Pediatric Treatment
  • Treatment options for childhood cancers.
• PDQ® Cancer Information Summaries: Supportive Care
  • Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.
• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)
  • Tests or procedures that detect specific types of cancer.
• PDQ® Cancer Information Summaries: Prevention
  • Risk factors and methods to increase chances of preventing specific types of cancer.
• PDQ® Cancer Information Summaries: Genetics
  • Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.
• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine
  • Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237) .