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Note: The Overview section summarizes the published evidence on this topic. The rest of the summary describes the evidence in more detail.
Other PDQ summaries containing information related to lung cancer screening include the following:
Evidence of Benefit Associated With Screening
Screening by low-dose computed tomography (LDCT): benefit
Two randomized trials have reported statistically significant reductions in lung cancer mortality associated with low-dose computed tomography (LDCT) screening. One trial reported that screening higher-risk individuals (30+ pack-years and either current smokers or quit within the past 15 years) aged 55 to 74 years three times, once annually, with LDCT reduced lung cancer mortality by 20% (95% confidence interval [CI], 6.8%–26.7%; P = .004) and all-cause mortality by 6.7% (95% CI, 1.2%–13.6%; P = .02) over screening with chest radiographs.[
Magnitude of Effect: About 20% to 24% relative reduction in lung cancer–specific mortality.
Study Design: Evidence obtained from randomized controlled trials (RCTs). |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Fair. |
Screening by LDCT: harms
False-positive exams
False-positive rates with LDCT screening have been high, although the magnitude of the rates varies with the definition of a positive screen.[
Magnitude of Effect: Two large randomized trials, the National Lung Screening Trial (NLST) and the Nederlands–Leuvens Longkanker Screenings Onderzoek Trial (NELSON), found that the average false-positive rate per screening round was 23.3% and 10.4%, respectively.[
Study Design: Evidence obtained from an RCT. |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Fair. |
Overdiagnosis from LDCT
Based on fair evidence, some lung cancers detected by LDCT screening appear to represent overdiagnosed cancer. However, estimates of overdiagnosis rates, derived typically by using data from randomized trials of LDCT screening, vary greatly. Therefore, the magnitude of overdiagnosis with LDCT screening is not clear. Overdiagnosed cancers result in unnecessary diagnostic procedures and also lead to unnecessary treatment. The harms of diagnostic procedures and treatment occur at the highest rate among long-term and/or heavy smokers because of smoking-associated comorbidities that increase risk propagation.
Magnitude of Effect: Uncertain.
Study Design: RCTs. |
Internal Validity: Good. |
Consistency: Evidence is consistent for the overall existence of overdiagnosis but is poor for determining the exact magnitude of effect. |
External Validity: Fair. |
Evidence of No Benefit Associated With Screening
Screening by chest x-ray and/or sputum cytology: benefits
Based on solid evidence, screening with chest x-ray and/or sputum cytology does not reduce mortality from lung cancer in the general population or in ever-smokers.
Magnitude of Effect: Not applicable.
Study Design: RCTs. |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Good. |
Screening by chest x-ray and/or sputum cytology: harms
False-positive exams
Based on solid evidence, false-positive rates with chest x-rays are in the range of 5% to 10% per exam. False-positive exams may result in unnecessary invasive diagnostic procedures.
Study Design: RCTs. |
Internal Validity: Good. |
Consistency: Good. |
External Validity: Good. |
Overdiagnosis from chest x-ray and/or sputum cytology
Based on fair evidence, some of the lung cancers detected by screening chest x-ray and/or sputum cytology appear to represent overdiagnosed cancer; however, the magnitude of overdiagnosis is not clear. These cancers result in unnecessary diagnostic procedures and also lead to unnecessary treatment. The harms of diagnostic procedures and treatment occur at the highest rate among long-term and/or heavy smokers because of smoking-associated comorbidities that increase risk propagation.
Magnitude of Effect: Uncertain.
Study Design: RCTs. |
Internal Validity: Good. |
Consistency: Evidence is consistent for the overall existence of overdiagnosis but is poor for determining the exact magnitude of effect. |
External Validity: Good. |
References:
Lung cancer is the second most common form of noncutaneous cancer in the United States and is the leading cause of cancer death in men and in women. In 2024 alone, it is estimated that 116,310 men and 118,270 women will be diagnosed with lung cancer, and 65,790 men and 59,280 women will die of this disease. The lung cancer death rate rose rapidly over several decades in both sexes, followed by a steady decline for men starting in 1991. From 2017 to 2021, death rates decreased by about 4% per year in both men and women.[
References:
The most important risk factor for lung cancer (as for many other cancers) is tobacco use.[
For a complete description of factors associated with an increased or decreased risk of lung cancer, see Lung Cancer Prevention.
References:
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).[
A systematic analysis [
Overall, lung cancer was diagnosed in 1.1% to 4.7% of screened participants; most of these diagnoses were early-stage disease.[
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.[
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.[
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.[
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.[
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.[
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.[
A
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.[
Another report used data from the NLST to address the question of whether the screening result influenced the likelihood of smoking cessation.[
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.[
The results of these studies suggest that the net impact of a CT program on smoking cessation varied,[
A meta-analysis that includes 85 RCTs published between 2010 and 2017 [
References:
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.[
In the early 1970s, the National Cancer Institute funded the Cooperative Early Lung Cancer Detection Program,[
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.[
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,[
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.[
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:
Screening by Low-Dose Computed Tomography
False-positive exams
False-positive exams are particularly problematic in the context of lung cancer screening. The individuals most likely to be screened for lung cancer, (i.e., heavy smokers) have comorbidities, such as chronic obstructive pulmonary disease and heart disease, that make them poor candidates for certain diagnostic procedures.
False-positive test results must be considered when lung cancer screening with low-dose computed tomography (LDCT) is being evaluated. A false-positive test may lead to anxiety and invasive diagnostic procedures, such as percutaneous needle biopsy or thoracotomy. The percentage of false-positive findings varies substantially among studies and is primarily attributable to differences in how a positive scan is defined (the size criteria), the thickness of the slice used between cuts (smaller slice thicknesses lead to detection of more nodules), and whether the subject resides in a geographic location where granulomatous disease is highly prevalent.
In the National Lung Screening Trial (NLST), the false-positive rate was 24% at baseline, and 27% and 16% for the two subsequent screening rounds.[
Diagnostic evaluations and downstream complications
A systematic review of the benefits and harms of computed tomography (CT) screening for lung cancer summarized 21 studies with respect to various diagnostic outcomes, although not all studies reported on all outcomes.[
In the NLST, most major complications were related to invasive procedures and surgeries performed on patients diagnosed with lung cancer, with a major complication rate of 11.8%. The rates of complications from the NLST may not be generalizable to a community setting; participants in the NLST were younger, better educated, and less likely to be current smokers (therefore, healthier) than the population of smokers and former smokers in the general U.S. population who would be eligible for screening. Of note, 82% of the participants were enrolled at large academic medical centers, and 76% of the participants were enrolled at National Cancer Institute–designated cancer centers. However, diagnostic follow-up did not necessarily occur at the NLST screening centers and could have been carried out in community settings. This may account for the low complication rate and surgical mortality rate (1%) found in the NLST. These findings led the multisociety position paper to strongly recommend that screening be carried out at centers with the same patient-management resources as those in the NLST.[
A retrospective cohort study of community practices indirectly estimated the complication rates and downstream medical costs of invasive diagnostic procedures performed for lung abnormalities identified through lung cancer screening.[
Overdiagnosis
A less familiar harm is overdiagnosis, which means the diagnosis of a condition that would not have become clinically significant had it not been detected by screening [
One approach to assessing overdiagnosis involves examining the volume-doubling time of lung tumors detected on LDCT. In one study, the volume-doubling times of 61 lung cancers were estimated by using an exponential model and successive CT images. Lesions were classified into the three following types: type G (ground glass opacity), type GS (focal glass opacity with a solid central component), and type S (solid nodule).
The mean volume-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, suggesting overdiagnosis.[
In a screening cohort with more than 5,000 participants, volume-doubling time was used as a surrogate for overdiagnosis. Patients with a calculated volume-doubling time of more than 400 days before surgical resection were considered to have a slow-growing or indolent cancer.[
Another approach to assessing overdiagnosis is to compare lung cancer incidence rates across arms in randomized trials of LDCT screening. Data from the NLST showed a gap of about 120 excess lung cancer cases in the LDCT group compared with the chest radiograph group after a medium follow-up of 6.5 years (i.e., 4.5 years after the last scheduled screen). This suggests that 18% of screen-detected lung cancers (N = 649) were overdiagnosed.[
Additional evidence of overdiagnosis with LDCT screening was observed in the randomized Danish Lung Cancer Screening Trial. At 10 years of follow-up (5 years after the last screening exam), almost twice as many lung cancers had been diagnosed in the screening group as in the control group: 5.1 vs. 2.7 cases per 1,000 person-years or 100 vs. 53 lung cancer cases in 4,104 total participants, respectively. Most of the lung cancers were early-stage adenocarcinomas, with no statistically significant difference in the number of stage III and IV cancers between the two groups.[
The overdiagnosis estimates from the NLST are compared with what would have been diagnosed with chest x-ray screening; therefore, in order to interpret them, it is necessary to have an estimate of the level of overdiagnosis using chest x-ray screening, preferably, covering a time period and population similar to those in the NLST. Such an estimate comes from the U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of chest x-ray screening versus usual care, specifically in the subset of PLCO trial participants who met the NLST eligibility criteria. These data showed no evidence of overdiagnosis, with essentially equivalent numbers of diagnosed lung cancers in the chest x-ray and usual-care arms after 3 years of follow-up after the last scheduled screen (rate ratio, 1.00).[
A meta-analysis of overdiagnosis from six randomized controlled trials, including the NLST and the NELSON, showed an aggregate overdiagnosis rate of 0.30 (95% CI, 0.06–0.55). The overdiagnosis rate was defined as the difference across arms in incident lung cancers divided by the number of screen-detected cases in the LDCT arm. However, there was significant heterogeneity (P = .0001) in the overdiagnosis rate across trials, with two small trials showing rates around 0.65 and the NLST showing a low rate of 0.04.[
Radiation exposure
Another potential risk from screening with LDCT is radiation exposure. The average exposure is low; the mean effective dose for LDCT in the NLST was 1.4 (SD = 0.5) mSv. It is estimated that over a 3-year period of screening, NLST participants were exposed to an average of 8 mSv of radiation (which accounts for radiation from screens and additional imaging for screen-detected nodules). A study of LDCT screens that were performed on more than 12,000 patients from 2016 to 2017 at 72 U.S. institutions found a mean effective dose of 1.2 (SD = 1.1) mSv. Almost two-thirds (65%) of the institutions had a median effective dose higher than the American College of Radiology guideline of 1 mSv. Modeling from previous work on radiation exposure and the development of cancer suggests that there could be one death per 2,500 screens in those participating in a screening program such as the NLST, although the benefit of screening of about one death avoided per 960 screens substantially outweighs the risk. Younger individuals and those without a significant risk of lung cancer may be more likely to suffer a radiation-induced lung cancer from screening than to be spared a lung cancer death.[
Screening by Chest X-ray and/or Sputum Cytology
False-positive exams
In the PLCO Cancer Screening Trial, the false-positive rate with chest x-ray screening ranged from 6.8% to 8.7% per exam over the four screening rounds.[
Diagnostic evaluation and downstream complications
In the NLST chest x-ray arm, among subjects with positive screens at baseline, 86% received imaging as diagnostic follow-up, 5% received a bronchoscopy, and 5% underwent a surgical procedure. Diagnostic imaging rates were modestly lower after postbaseline positive screens, while bronchoscopy and surgery rates were similar. A total of 0.3% of false-positive screens were associated with a complication of an invasive diagnostic procedure.[
In the PLCO trial, 0.4% of participants with at least one false-positive screen who had a diagnostic evaluation had a complication associated with a diagnostic procedure.[
Overdiagnosis
In the Mayo Lung Project trial of screening with chest x-ray and sputum cytology, after 5 years of follow-up after the last scheduled screen, 206 cancers were diagnosed in the screening arm compared with 160 cancers in the control arm.[
References:
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.
Incidence and Mortality
Updated statistics with estimated new cases and deaths for 2024 (cited American Cancer Society as reference 1). Also revised text to state that from 2017 to 2021, death rates decreased by about 4% per year in both men and women.
This summary is written and maintained by the
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.
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PDQ® Screening and Prevention Editorial Board. PDQ Lung Cancer Screening. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at:
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