Evidence of Benefit Associated With Screening

Evidence of No Benefit Associated With Screening

References

1. Aberle DR, Adams AM, Berg CD, et al.: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365 (5): 395-409, 2011. [PMC free article: PMC4356534] [PubMed: 21714641]
2. Pinsky PF, Church TR, Izmirlian G, et al.: The National Lung Screening Trial: results stratified by demographics, smoking history, and lung cancer histology. Cancer 119 (22): 3976-83, 2013. [PMC free article: PMC3936005] [PubMed: 24037918]
3. de Koning HJ, van der Aalst CM, de Jong PA, et al.: Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med 382 (6): 503-513, 2020. [PubMed: 31995683]
4. Pinsky PF, Gierada DS, Black W, et al.: Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment. Ann Intern Med 162 (7): 485-91, 2015. [PMC free article: PMC4705835] [PubMed: 25664444]

References

1. American Cancer Society: Cancer Facts and Figures 2022. American Cancer Society, 2022. Available online. Last accessed October 7, 2022.

References

1. The Health Consequences of Smoking: A Report of the Surgeon General. U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, 2004. Also available online. Last accessed April 11, 2023.
2. Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service. US Department of Health, Education, and Welfare, 1965. PHS Publ No 1103.

Screening by Low-Dose Computed Tomography

There have been intensive efforts to improve lung cancer screening with newer technologies, including low-dose computed tomography (LDCT).[1,2] LDCT was shown to be more sensitive than chest radiography. In the Early Lung Cancer Action Project (ELCAP),[2] LDCT detected almost six times as many stage I lung cancers as chest radiography, and most of these tumors were no larger than 1 cm in diameter.

A systematic analysis [3] summarized 13 observational studies of LDCT, which included 60 to 5,201 participants and were conducted between 1993 and 2004. Some Japanese studies included nonsmokers, but the other studies were limited to current and former smokers. Variability in detection of nodules—between 3% and 51%—may be attributed to several factors:

• The definition of nodules (some studies required a size threshold).
• The computed tomography (CT) technology (thin slice detects more and smaller nodules).
• Geographic variation in endemic granulomatous disease.

Overall, lung cancer was diagnosed in 1.1% to 4.7% of screened participants; most of these diagnoses were early-stage disease.[3]

The National Lung Screening Trial (NLST) provided the first solid evidence that screening with LDCT can reduce lung cancer mortality risk in ever-smokers who have smoked 30 pack-years or longer and in former smokers who have quit within the past 15 years. The NLST included 33 centers across the United States. Eligible participants were between the ages of 55 years and 74 years at randomization, had a history of at least 30 pack-years of cigarette smoking, and, if former smokers, had quit within the past 15 years. A total of 53,454 individuals were enrolled; 26,722 participants were randomly assigned to receive screening with LDCT, and 26,732 participants were randomly assigned to receive screening with chest x-ray. Any noncalcified nodule found with LDCT that measured at least 4 mm in any diameter and any noncalcified nodule or mass identified on x-ray images were classified as positive. Radiologists, however, had the option of calling a final screen negative if a noncalcified nodule had been stable on the three screening exams. The LDCT group had a substantially higher rate of positive screening tests than did the radiography group (round 1, 27.3% vs. 9.2%; round 2, 27.9% vs. 6.2%; and round 3, 16.8% vs. 5.0%). Overall, 39.1% of participants in the LDCT group and 16.0% in the radiography group had at least one positive screening result. Of those who screened positive, the proportion with lung cancer (i.e., positive predictive value) was 3.6% in the LDCT group and 5.5% in the radiography group.[4]

In the LDCT group, 649 cancers were diagnosed after a positive screening test, 44 after a negative screening test, and 367 among participants who either missed the screening or received the diagnosis after the completion of the screening phase. In the radiography group, 279 cancers were diagnosed after a positive screening test, 137 after a negative screening test, and 525 among participants who either missed the screening or received the diagnosis after the completion of the screening phase. Three hundred fifty-six deaths from lung cancer occurred in the LDCT group, and 443 deaths from lung cancer occurred in the chest x-ray group; the relative reduction in the rate of death from lung cancer was 20% (95% confidence interval [CI], 6.8%–26.7%) with LDCT screening at a median duration of follow-up of 6.5 years.[4] An updated analysis showed that the estimated reduction in lung cancer mortality was 16% (95% CI, 5%–25%).[5] Overall, mortality was reduced by 6.7% (95% CI, 1.2%–13.6%). The number needed to screen with LDCT to prevent one death from lung cancer was 320.[4]

An extended follow-up analysis of the NLST reported mortality data after a median of 12.3 years of follow-up. The estimated number needed to screen with LDCT to prevent one lung cancer death was 303.[6]

Since the publication of the results of the NLST, more has been learned about who may benefit the most from screening for lung cancer using LDCT.[7-9] One group of investigators developed an individual risk model to assess who might benefit from screening. The model used additional factors not used as inclusion criteria in the NLST, such as a history of chronic obstructive pulmonary disease, personal or family history of lung cancer, and a more detailed smoking history. More individuals would have been eligible to be screened using the trial's criteria as opposed to the inclusion criteria of the NLST without missing patients with cancer.[8] A second group performed a reanalysis of the NLST data, calculated each patient’s risk of developing lung cancer, and estimated each patient's lung cancer mortality.[9] The investigators then divided the NLST participants into five groups on the basis of risk. The number needed to screen to avoid a lung cancer death in the low-risk group was 5,276; 161 screens were needed in the high-risk group to avoid a lung cancer death. Furthermore, the number of false-positive screens decreased from 1,648 in the lowest quintile of risk to 65 in the highest-risk group. The three highest quintiles of risk accounted for 88% of the mortality reduction from screening, whereas the lowest quintile accounted for only a 1% reduction in mortality. These studies illustrate possible improvements for determining the population of patients who may benefit the most from screening, potentially reducing the number of false positives and reducing the potential harm related to the adverse events associated with their evaluation. One other benefit of calculating individual risk is the ability to incorporate the findings into a shared decision-making process so that patients can decide whether to undergo screening.[9] However, a comparison of ten models used for predicting lung cancer or lung cancer mortality risk found that four of the models were well calibrated with reasonable discrimination, but none of these models were considered superior to the others for identifying lung cancer risk among individuals who had ever smoked. Additional work is needed to address modeling weaknesses.[10]

The NELSON trial (Nederlands–Leuvens Longkanker Screenings Onderzoek) conducted in Belgium and the Netherlands examined screening for lung cancer in smokers (13,195 men, 2,594 women, and 3 unknown) with CT, using a volume criterion for positivity.[11] Participants were recruited from population registries in the two countries based on responses to questionnaires about their smoking history and other data. Those who either smoked currently or had quit for fewer than 10 years and had smoked more than 15 cigarettes a day for over 25 years or more than 10 cigarettes a day for over 30 years were eligible. Those with serious comorbidities or previous cancers were excluded. All participants were randomly assigned equally to either usual care or an initial screen and three subsequent screens at intervals of 1, 2, and 2.5 years. The screening test was LDCT, which was retrospectively analyzed by supervised software to determine nodule segmentation and volume. After a minimum follow-up of 10 years, 90% of men assigned to screening complied with each opportunity on average, with a 2.1% rate of being referred for diagnosis. These men experienced a lung cancer incidence rate of 5.58 per 1,000 person-years and a lung cancer–specific mortality rate of 2.5 per 1,000 person-years, compared with 4.91 cases and 3.3 deaths per 1,000 person-years in men assigned to usual care. The mortality rate ratio for screening was 0.76 (95% CI, 0.61–0.94).[11]

Although the NELSON study used a usual-care arm instead of a chest x-ray arm, the results are consistent with the main NLST results discussed above, both in the impact on lung cancer mortality and in overdiagnosis. The mortality results were even more similar when the NELSON cohort was constrained to the NLST smoking eligibility subgroup. The two studies diverged in several ways, however. The NLST observed an all-cause mortality reduction consistent with the dominant effect of lung cancer on mortality among smokers. NELSON did not find such an effect. In addition, no healthy volunteer effect was observed in NELSON, while the NLST reported a substantial effect. However, these differences between the studies do not cast doubt on the main effect on lung cancer mortality but may invite further analyses to understand the inconsistencies better.

Other, smaller randomized clinical trials (RCTs) of LDCT that compare a nonscreening arm with LDCT are under way or are already completed in a number of countries.[12- 18] These smaller trials are not powered to assess mortality as an endpoint, but there is an effort to combine the findings from these studies with the NELSON data, once the data are fully mature. These studies may also assess consistency with the NLST findings. In addition to the data gleaned from ongoing trials, data from the NLST, NELSON, and other completed trials are being analyzed to examine other important issues in lung cancer screening, including cost-effectiveness, quality of life, and whether screening would benefit individuals younger than those enrolled in the NLST and those with fewer than 30 pack-years of smoking exposure. Data from the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial suggest that, in the absence of screening, the risk of lung cancer death for current smokers who have a smoking history of 20 to 29 pack-years is no different from that of former smokers who have quit within 15 years and have a smoking history of more than 30 pack-years (hazard ratio, 1.07; CI, 0.75–1.5).[19] Although the risk for the 20-to-29-pack-years current-smokers group is no different from that of the former-smokers group (for whom LDCT screening is recommended by the U.S. Preventive Services Task Force), the efficacy of screening is unknown in the 20-to-29-pack-years current-smokers group.[19]

[Note: A Guide has been developed to help patients and physicians assess the benefits and harms of LDCT screening for lung cancer.[20]]

Screening and Smoking Cessation

The target population for lung cancer screening has a high prevalence of current smokers compared with the general population. A lung cancer screening program could potentially impact the likelihood of smoking cessation, theoretically promoting cessation among those screened who have lung abnormalities detected on their screen. Conversely, screening could also be a deterrent to cessation among those with no evidence of lung abnormalities on their screen. The Danish Lung Cancer Screening Trial is a randomized trial that compared LDCT with no intervention among participants aged 50 to 70 years who had at least a 20 pack-year smoking history.[21] The proportion of participants who had quit smoking was monitored every year for 5 years of follow-up and remained virtually identical in the two groups from baseline (CT group and control group each had 23% ex-smokers) until the 5-year follow-up (43% ex-smokers in both groups). The comparison of these two randomized groups indicates that the CT screening program had zero net effect on the likelihood of smoking cessation.

Another report used data from the NLST to address the question of whether the screening result influenced the likelihood of smoking cessation.[22] The NLST compared CT with chest x-ray, and data from both arms were pooled to examine the impact of abnormal findings on the likelihood of smoking cessation. Compared with those who did not have abnormal findings, current smokers who had a screening examination that was suspicious for lung cancer (but was not lung cancer) were significantly more likely to have stopped smoking 1 year later. The associations with quitting smoking among those who had a major lung abnormality that was not suspicious for lung cancer, or those who had a minor abnormality, were weaker and not uniformly statistically significant.

A third study from the U.K. Lung Cancer Screening pilot trial of an LDCT scan found that screening was associated with a statistically significant increase in short- and long-term cessation, and this effect was greatest among those whose initial screening test was positive, warranting additional clinical investigation.[23]

The results of these studies suggest that the net impact of a CT program on smoking cessation varied,[21] but there appears to be a higher likelihood of smoking cessation among current smokers who have findings suspicious for lung cancer.[22] This is an important research area that needs to be clarified.

A meta-analysis that includes 85 RCTs published between 2010 and 2017 [24] concluded that electronic/Web-based, in-person counseling, and pharmacotherapy treatment interventions significantly increased the odds of successful smoking cessation among populations eligible for lung cancer screening.

References

1. 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. [PubMed: 10050866]
2. 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. [PubMed: 10408484]
3. Bach PB, Mirkin JN, Oliver TK, et al.: Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 307 (22): 2418-29, 2012. [PMC free article: PMC3709596] [PubMed: 22610500]
4. Aberle DR, Adams AM, Berg CD, et al.: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365 (5): 395-409, 2011. [PMC free article: PMC4356534] [PubMed: 21714641]
5. Pinsky PF, Church TR, Izmirlian G, et al.: The National Lung Screening Trial: results stratified by demographics, smoking history, and lung cancer histology. Cancer 119 (22): 3976-83, 2013. [PMC free article: PMC3936005] [PubMed: 24037918]
6. National Lung Screening Trial Research Team: Lung Cancer Incidence and Mortality with Extended Follow-up in the National Lung Screening Trial. J Thorac Oncol 14 (10): 1732-1742, 2019. [PMC free article: PMC6764895] [PubMed: 31260833]
7. Moyer VA; U.S. Preventive Services Task Force: Screening for lung cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 160 (5): 330-8, 2014. [PubMed: 24378917]
8. Tammemägi MC, Katki HA, Hocking WG, et al.: Selection criteria for lung-cancer screening. N Engl J Med 368 (8): 728-36, 2013. [PMC free article: PMC3929969] [PubMed: 23425165]
9. Kovalchik SA, Tammemagi M, Berg CD, et al.: Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med 369 (3): 245-54, 2013. [PMC free article: PMC3783654] [PubMed: 23863051]
10. Katki HA, Kovalchik SA, Petito LC, et al.: Implications of Nine Risk Prediction Models for Selecting Ever-Smokers for Computed Tomography Lung Cancer Screening. Ann Intern Med 169 (1): 10-19, 2018. [PMC free article: PMC6557386] [PubMed: 29800127]
11. de Koning HJ, van der Aalst CM, de Jong PA, et al.: Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial. N Engl J Med 382 (6): 503-513, 2020. [PubMed: 31995683]
12. Paci E, Puliti D, Lopes Pegna A, et al.: Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial. Thorax 72 (9): 825-831, 2017. [PubMed: 28377492]
13. Wille MM, Dirksen A, Ashraf H, et al.: Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling. Am J Respir Crit Care Med 193 (5): 542-51, 2016. [PubMed: 26485620]
14. Infante M, Cavuto S, Lutman FR, et al.: Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography. Am J Respir Crit Care Med 191 (10): 1166-75, 2015. [PubMed: 25760561]
15. Pastorino U, Rossi M, Rosato V, et al.: Annual or biennial CT screening versus observation in heavy smokers: 5-year results of the MILD trial. Eur J Cancer Prev 21 (3): 308-15, 2012. [PubMed: 22465911]
16. Pastorino U, Silva M, Sestini S, et al.: Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol 30 (7): 1162-1169, 2019. [PMC free article: PMC6637372] [PubMed: 30937431]
17. Doria-Rose VP, Szabo E: Screening and prevention of lung cancer. In: Kernstine KH, Reckamp KL, eds.: Lung Cancer: A Multidisciplinary Approach to Diagnosis and Management. Demos Medical, 2011, pp 53-72.
18. Becker N, Motsch E, Trotter A, et al.: Lung cancer mortality reduction by LDCT screening-Results from the randomized German LUSI trial. Int J Cancer 146 (6): 1503-1513, 2020. [PubMed: 31162856]
19. Pinsky PF, Kramer BS: Lung Cancer Risk and Demographic Characteristics of Current 20-29 Pack-year Smokers: Implications for Screening. J Natl Cancer Inst 107 (11): , 2015. [PMC free article: PMC4849359] [PubMed: 26483244]
20. Woloshin S, Schwartz LM, Black WC, et al.: Cancer screening campaigns--getting past uninformative persuasion. N Engl J Med 367 (18): 1677-9, 2012. [PubMed: 23113476]
21. Ashraf H, Saghir Z, Dirksen A, et al.: Smoking habits in the randomised Danish Lung Cancer Screening Trial with low-dose CT: final results after a 5-year screening programme. Thorax 69 (6): 574-9, 2014. [PubMed: 24443174]
22. Tammemägi MC, Berg CD, Riley TL, et al.: Impact of lung cancer screening results on smoking cessation. J Natl Cancer Inst 106 (6): dju084, 2014. [PMC free article: PMC4081623] [PubMed: 24872540]
23. Brain K, Carter B, Lifford KJ, et al.: Impact of low-dose CT screening on smoking cessation among high-risk participants in the UK Lung Cancer Screening Trial. Thorax 72 (10): 912-918, 2017. [PMC free article: PMC5738533] [PubMed: 28710339]
24. Cadham CJ, Jayasekera JC, Advani SM, et al.: Smoking cessation interventions for potential use in the lung cancer screening setting: A systematic review and meta-analysis. Lung Cancer 135: 205-216, 2019. [PMC free article: PMC6739236] [PubMed: 31446996]

Screening by Chest X-ray and/or Sputum Cytology

The question of lung cancer screening dates back to the 1950s, when rising lung cancer incidence and mortality rates indicated a need for intervention. In response to the emerging lung cancer problem, five studies of chest imaging, two of which were controlled, were undertaken during the 1950s and 1960s.[1-8] Two studies also included sputum cytology.[1-5] The results of these studies suggested no overall benefit of screening, although design limitations prevented the studies from providing definitive evidence.

In the early 1970s, the National Cancer Institute funded the Cooperative Early Lung Cancer Detection Program,[9] which was designed to assess the ability of screening with radiologic chest imaging and sputum cytology to reduce lung cancer mortality in male smokers. The program comprised three separate randomized controlled trials (RCTs), each enrolling about 10,000 male participants aged 45 years and older who smoked at least one pack of cigarettes a day in the previous year. One study was conducted at the Mayo Clinic,[10-12] one at Johns Hopkins University,[13-15] and one at Memorial Sloan-Kettering Cancer Center.[15-18] The Hopkins and Sloan-Kettering studies employed the same design: participants randomly assigned to the intervention arm received sputum cytology every 4 months and annual chest imaging, while participants randomly assigned to the control arm received annual chest imaging. Neither study observed a reduction in lung cancer mortality with screening.[15] The two studies were interpreted as showing no benefit of frequent sputum cytology when added to an annual regimen of chest x-ray.

The design of the Mayo Clinic study (known as the Mayo Lung Project, or MLP), was different. All potential participants were screened with chest imaging and sputum cytology, and those known or suspected to have lung cancer, as well as those in poor health, were excluded. Remaining participants were randomly assigned to either an intervention arm that received chest imaging and sputum cytology every 4 months for 6 years, or to a control arm that received a one-time recommendation at trial entry to receive the same tests on an annual basis. No reduction in lung cancer mortality was observed. The MLP was interpreted in the 1970s as showing no benefit of an intense screening regimen with chest x-ray and sputum cytology.

One RCT of lung cancer screening with chest imaging was conducted in Europe in the 1970s. This Czechoslovakian study began with a prevalence screen (chest imaging and sputum cytology) of 6,364 men aged 40 to 64 years who were current smokers with a lifetime consumption of at least 150,000 cigarettes.[19,20] All participants except the 18 diagnosed with lung cancer as a result of the prevalence screen were randomly assigned to either an intervention arm or a control arm. Participants in the intervention arm received semiannual screening for 3 years. Participants in the control arm received screening during the third year only. The investigators reported 19 lung cancer deaths in the intervention arm and 13 in the control arm. They concluded that frequent screening was not necessary.

By 1990, the medical community was still unsure about the relationship between screening with chest imaging (using traditional chest x-ray) and lung cancer mortality. Although previous studies showed no benefit, findings were not definitive because of a lack of statistical power. A multiphasic trial with ample statistical power, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial,[21] began in 1992. PLCO enrolled 154,901 participants aged 55 to 74 years, including women (50%) and never-smokers (45%). One-half of the participants were randomly assigned to screening, and the other half of them were advised to receive their usual medical care. PLCO had 90% power to detect a 20% reduction in lung cancer mortality.

The lung component of PLCO addressed the question of whether annual single-view (posterior-anterior) chest x-ray was capable of reducing lung cancer mortality as compared with usual medical care. When the study began, all participants randomly assigned to screening were invited to receive a baseline and three annual chest x-ray screens, although the protocol ultimately was changed to screen never-smokers only three times. At 13 years of follow-up, 1,213 lung cancer deaths were observed in the intervention group, compared with 1,230 lung cancer deaths in the usual-care group (mortality relative risk, 0.99; 95% confidence interval, 0.87–1.22). Subanalyses suggested no differential effect by sex or smoking status.[21]

Given the abundance and consistency of evidence, as well as the lack of benefit observed in the PLCO trial, it is appropriate to conclude that lung cancer screening with chest x-ray and/or sputum cytology, regardless of sex or smoking status, does not reduce lung cancer mortality.

References

1. 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. [PubMed: 5922259]
2. Boucot KR, Weiss W: Is curable lung cancer detected by semiannual screening? JAMA 224 (10): 1361-5, 1973. [PubMed: 4739985]
3. Brett GZ: The value of lung cancer detection by six-monthly chest radiographs. Thorax 23 (4): 414-20, 1968. [PMC free article: PMC471810] [PubMed: 5664703]
4. Brett GZ: Earlier diagnosis and survival in lung cancer. Br Med J 4 (678): 260-2, 1969. [PMC free article: PMC1629689] [PubMed: 5345935]
5. Dales LG, Friedman GD, Collen MF: Evaluating periodic multiphasic health checkups: a controlled trial. J Chronic Dis 32 (5): 385-404, 1979. [PubMed: 109452]
6. Nash FA, Morgan JM, Tomkins JG: South London Lung Cancer Study. Br Med J 2 (607): 715-21, 1968. [PMC free article: PMC1991645] [PubMed: 5690439]
7. Weiss W, Boucot KR, Cooper DA: The Philadelphia pulmonary neoplasm research project. Survival factors in bronchogenic carcinoma. JAMA 216 (13): 2119-23, 1971. [PubMed: 5108675]
8. Weiss W, Boucot KR: The Philadelphia Pulmonary Neoplasm Research Project. Early roentgenographic appearance of bronchogenic carcinoma. Arch Intern Med 134 (2): 306-11, 1974. [PubMed: 4843198]
9. Berlin NI: Overview of the NCI Cooperative Early Lung Cancer Detection Program. Cancer 89 (11 Suppl): 2349-51, 2000. [PubMed: 11147610]
10. Fontana RS, Sanderson DR, Taylor WF, et al.: Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Mayo Clinic study. Am Rev Respir Dis 130 (4): 561-5, 1984. [PubMed: 6091507]
11. Fontana RS, Sanderson DR, Woolner LB, et al.: Lung cancer screening: the Mayo program. J Occup Med 28 (8): 746-50, 1986. [PubMed: 3528436]
12. Fontana RS, Sanderson DR, Woolner LB, et al.: Screening for lung cancer. A critique of the Mayo Lung Project. Cancer 67 (4 Suppl): 1155-64, 1991. [PubMed: 1991274]
13. Frost JK, Ball WC, Levin ML, et al.: Early lung cancer detection: results of the initial (prevalence) radiologic and cytologic screening in the Johns Hopkins study. Am Rev Respir Dis 130 (4): 549-54, 1984. [PubMed: 6091505]
14. 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. [PubMed: 7111836]
15. Doria-Rose VP, Marcus PM, Szabo E, et al.: Randomized controlled trials of the efficacy of lung cancer screening by sputum cytology revisited: a combined mortality analysis from the Johns Hopkins Lung Project and the Memorial Sloan-Kettering Lung Study. Cancer 115 (21): 5007-17, 2009. [PMC free article: PMC2767423] [PubMed: 19637354]
16. Flehinger BJ, Kimmel M, Polyak T, et al.: Screening for lung cancer. The Mayo Lung Project revisited. Cancer 72 (5): 1573-80, 1993. [PubMed: 8394199]
17. Melamed M, Flehinger B, Miller D, et al.: Preliminary report of the lung cancer detection program in New York. Cancer 39 (2): 369-82, 1977. [PubMed: 837325]
18. 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. [PubMed: 6734291]
19. Kubík A, Polák J: Lung cancer detection. Results of a randomized prospective study in Czechoslovakia. Cancer 57 (12): 2427-37, 1986. [PubMed: 3697941]
20. 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. [PubMed: 2404878]
21. Oken MM, Hocking WG, Kvale PA, et al.: Screening by chest radiograph and lung cancer mortality: the Prostate, Lung, Colorectal, and Ovarian (PLCO) randomized trial. JAMA 306 (17): 1865-73, 2011. [PubMed: 22031728]

Screening by Low-Dose Computed Tomography

Screening by Chest X-ray and/or Sputum Cytology

References

1. Aberle DR, Adams AM, Berg CD, et al.: Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 365 (5): 395-409, 2011. [PMC free article: PMC4356534] [PubMed: 21714641]
2. Bach PB, Mirkin JN, Oliver TK, et al.: Benefits and harms of CT screening for lung cancer: a systematic review. JAMA 307 (22): 2418-29, 2012. [PMC free article: PMC3709596] [PubMed: 22610500]
3. Pinsky PF, Gierada DS, Black W, et al.: Performance of Lung-RADS in the National Lung Screening Trial: a retrospective assessment. Ann Intern Med 162 (7): 485-91, 2015. [PMC free article: PMC4705835] [PubMed: 25664444]
4. Mazzone P, Powell CA, Arenberg D, et al.: Components necessary for high-quality lung cancer screening: American College of Chest Physicians and American Thoracic Society Policy Statement. Chest 147 (2): 295-303, 2015. [PMC free article: PMC4502754] [PubMed: 25356819]
5. Huo J, Xu Y, Sheu T, et al.: Complication Rates and Downstream Medical Costs Associated With Invasive Diagnostic Procedures for Lung Abnormalities in the Community Setting. JAMA Intern Med 179 (3): 324-332, 2019. [PMC free article: PMC6440230] [PubMed: 30640382]
6. Black WC: Overdiagnosis: An underrecognized cause of confusion and harm in cancer screening. J Natl Cancer Inst 92 (16): 1280-2, 2000. [PubMed: 10944539]
7. 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. [PubMed: 2787730]
8. Dammas S, Patz EF, Goodman PC: Identification of small lung nodules at autopsy: implications for lung cancer screening and overdiagnosis bias. Lung Cancer 33 (1): 11-6, 2001. [PubMed: 11429191]
9. Marcus PM, Fagerstrom RM, Prorok PC, et al.: Screening for lung cancer with helical CT scanning. Clinical Pulmonary Medicine 9 (6): 323-9, 2002.
10. 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. [PubMed: 11205667]
11. Veronesi G, Maisonneuve P, Bellomi M, et al.: Estimating overdiagnosis in low-dose computed tomography screening for lung cancer: a cohort study. Ann Intern Med 157 (11): 776-84, 2012. [PubMed: 23208167]
12. Patz EF, Pinsky P, Gatsonis C, et al.: Overdiagnosis in low-dose computed tomography screening for lung cancer. JAMA Intern Med 174 (2): 269-74, 2014. [PMC free article: PMC4040004] [PubMed: 24322569]
13. Wille MM, Dirksen A, Ashraf H, et al.: Results of the Randomized Danish Lung Cancer Screening Trial with Focus on High-Risk Profiling. Am J Respir Crit Care Med 193 (5): 542-51, 2016. [PubMed: 26485620]
14. Heleno B, Siersma V, Brodersen J: Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography Screening: A Secondary Analysis of the Danish Lung Cancer Screening Trial. JAMA Intern Med 178 (10): 1420-1422, 2018. [PMC free article: PMC6233751] [PubMed: 30276415]
15. Paci E, Puliti D, Lopes Pegna A, et al.: Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial. Thorax 72 (9): 825-831, 2017. [PubMed: 28377492]
16. Infante M, Cavuto S, Lutman FR, et al.: Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography. Am J Respir Crit Care Med 191 (10): 1166-75, 2015. [PubMed: 25760561]
17. Pastorino U, Silva M, Sestini S, et al.: Prolonged lung cancer screening reduced 10-year mortality in the MILD trial: new confirmation of lung cancer screening efficacy. Ann Oncol 30 (7): 1162-1169, 2019. [PMC free article: PMC6637372] [PubMed: 30937431]
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Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about lung cancer screening. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Screening and Prevention Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

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The preferred citation for this PDQ summary is:

PDQ® Screening and Prevention Editorial Board. PDQ Lung Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lung/hp/lung-screening-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389268]

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Disclaimer

The information in these summaries should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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