Lung Cancer and Low-Dose CT Screening — Reading a Small Spot in the Picture Over Time

"They Say They Found a Small Spot on the CT"

Your father, who smoked for a long time, had a chest CT during a health checkup. When you went to hear the results, you were told, "There is a small spot visible in the lung." Meanwhile, you hear that a neighbor who has never touched a cigarette was diagnosed with lung cancer. The saying that smoking causes lung cancer is familiar, but the idea of getting it without smoking and the story of a spot on a checkup scan feel unfamiliar.

The lungs are organs located one on each side inside the chest, exchanging oxygen and carbon dioxide between inhaled air and blood. Lung cancer is cancer that begins in the lungs, a disease where lung cells multiply out of control and form a mass. Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide, with an estimated 2 million people diagnosed and 1.8 million dying each year (PMID 33911981). In Korea as well, lung cancer claims the most lives among people dying from cancer (PMID 27064578).

This article traces where lung cancer comes from and what branches it divides into, alongside what screening CT scans look for and what trade-offs they bring. In the screening section, we draw on large-scale trials from the US and Europe, the pilot lung cancer screening project and national lung cancer screening conducted in Korea, and Korean data.

A Disease That Reveals Itself Late and Splits in Two

Most people diagnosed with lung cancer are diagnosed only after the disease has already progressed. This is because symptoms appear late and screenings are not performed sufficiently, and as a result, the prognosis is quite poor (PMID 27188576).

When symptoms are present, they may include wheezing, chest pain, shortness of breath, and bloody phlegm, and bone pain or headaches may also occur due to cancer that has spread to other places. They are also sometimes discovered incidentally on images taken for other reasons (PMID 41114991). Metastasis refers to cancer cells leaving their original site, moving to other organs, and growing there again. Bone pain and headaches are symptoms created by cancer that has migrated in this way. These symptoms also appear in diseases that are not lung cancer, so lung cancer cannot be distinguished by symptoms alone. Diagnosis is made with imaging such as X-rays, CT, and PET, and examinations that look at removed tissue under a microscope (PMID 27188576).

Lung cancer is largely divided into two branches depending on the appearance of the cancer cells seen under a microscope, and the two branches grow and spread in different ways (PMID 26297204). Small-cell lung cancer is lung cancer made up of small cells when viewed under a microscope. Non-small-cell lung cancer is a name that groups together lung cancers that are not small-cell lung cancer, and the majority of lung cancers fall into this category. About 85% of newly diagnosed lung cancers are non-small-cell lung cancer (PMID 27188576).

Adenocarcinoma is a cancer made of cancer cells resembling gland-forming cells, and is the most common branch among lung cancers. Adenocarcinoma belongs to non-small-cell lung cancer (PMID 21252716). In Korea too, adenocarcinoma has steadily increased, surpassing squamous cell carcinoma, which was previously the most common, to become the most common lung cancer (PMID 27064578). The reason for dividing the branches lies in treatment. Which treatment is right depends on the branch and the degree of spread of the lung cancer (PMID 26297204).

Tobacco, and Causes Outside of Tobacco

Tobacco is the single biggest cause of lung cancer. It is estimated that up to 90% of lung cancers are due to smoking (PMID 33911981), and smoking raises the risk of lung cancer by 5 to 10 times, with the risk growing the more one smokes (PMID 26667337).

Secondhand smoke is the act of breathing in tobacco smoke exhaled by someone else while not smoking oneself. When about 80 studies covering nonsmokers are pooled together, the lung cancer risk for people exposed to secondhand smoke was 24% higher than for those not exposed, and the risk grew greater the longer the duration and the greater the amount of exposure. The authors concluded that this is definitive evidence showing an association between secondhand smoke and lung cancer risk in nonsmokers (PMID 39537242). In an analysis pooling only women who did not smoke, this risk was 31% higher in Asia and 13% higher in Europe and the Americas, making it larger in Asia (PMID 41855613). Because 24% or 31% is a relative magnitude compared against the risk in unexposed people, how many actual people that difference translates to for someone with a low baseline risk must be counted separately.

Radon is a radioactive gas produced when uranium in the ground naturally decays. Radon leaks out of soil and rock and accumulates in closed spaces with poor ventilation (PMID 21199598). Radon is cited as the second-leading cause of lung cancer after smoking (PMID 33911981, PMID 31250572), and is cited as the single largest risk factor globally for lung cancer in nonsmokers (PMID 33536262). The relationship in which higher indoor radon concentrations increase lung cancer risk was seen in both nonsmokers and smokers (PMID 33536262).

Asbestos, diesel exhaust, and ionizing radiation inhaled in the workplace are also known risk factors, and having a family member who had lung cancer or having a history of chronic obstructive pulmonary disease are likewise associated with lung cancer risk (PMID 26667337). Family history is reported to raise the risk by 1.7 times (PMID 33911981). Air pollution is also cited as a factor associated with lung cancer (PMID 33911981), and in East Asia, there are reports that exposure to fine particulate matter is associated with the incidence and mortality of lung cancer in nonsmokers (PMID 41932615). A 2016 review stated that the risk of e-cigarettes was not yet consistently established, and a 2021 review also notes that they remain at the hypothesis stage of potentially increasing risk (PMID 26667337, PMID 33911981).

Lung Cancer in People Who Do Not Smoke

Non-smokers usually refer to people who have smoked fewer than 100 cigarettes in their lifetime. Lung cancer occurring in them accounts for 15 to 20% of global lung cancer, 60 to 80% of which is adenocarcinoma, while small cell lung cancer is rare (PMID 41114991).

This share is much larger in East Asia. In some groups in East Asia, particularly women, non-smoker lung cancer accounts for over 60% of diagnosed lung cancer (PMID 42166705). In registry data collecting about 10% of Korean lung cancer cases, 87.5% of 735 female lung cancer patients with confirmed smoking histories were non-smokers (PMID 33145034). There is also a review stating that non-smokers in Asia have a 2.3 times higher lung cancer incidence than non-smokers outside Asia (PMID 41932615).

Why it is common among East Asian women has not been settled as a single reason. There is a hypothesis that indoor coal burning, cooking smoke, and infections may play important roles in non-smoking Asian women (PMID 21527061). Inherent genetic differences are also discussed. Most genetic variants newly found in adenocarcinomas of East Asian people showed no association in European people (PMID 37236969). A 2009 review summarized that while several environmental, genetic, hormonal, and viral factors were associated with non-smoker lung cancer, none reached definitive evidence (PMID 19532009). Afterward, a 2024 meta-analysis concluded that secondhand smoke showed definitive evidence for an association with non-smoker lung cancer (PMID 39537242), and a 2021 meta-analysis on radon showed a relationship where higher indoor concentrations increased the risk (PMID 33536262). However, in this radon meta-analysis, the side with greater risk among non-smokers was men (PMID 33536262), and evidence explaining why these two account for why it is common in East Asian women is not in the data gathered by this article.

There are reports that the incidence of non-smoker lung cancer is increasing (PMID 41932615). On the other hand, a 2008 analysis gathering 13 large cohorts produced results inconsistent with claims that the risk for non-smokers is rising and that the incidence in women is higher than in men, and stated that the high and fluctuating incidence in women across the Pacific Rim, including East Asia, requires further study (PMID 18788891). Because the two sources differ in time period and subjects, the evidence gathered by this article cannot determine which side is correct. Also, the share of non-smokers among lung cancer cases growing larger and the risk for an individual non-smoker growing larger are different stories.

Stage — How Far Has It Spread?

Stage divides how much the cancer has grown from where it first started and how far it has spread into several steps. To decide which treatment is right, you need to know the stage accurately (PMID 27188576). When a cancer is diagnosed at an earlier stage, people tend to live longer (PMID 27535387).

The 5-year survival rate is the proportion of people diagnosed with a disease who are still alive 5 years later. In the United States, the overall 5-year survival rate for lung cancer is 20.5%, and lung cancer caught at an early stage has a better prognosis and is easier to manage with treatment (PMID 33687470). Within South Korea, the 5-year relative survival rate for lung cancer rose from 11.3% in 1993–1995 to 30.2% in 2013–2017, which is thought to be thanks to improvements in diagnostic and treatment methods (PMID 33587838). Relative survival rate is a value compared against the fraction of the general population of the same age and sex who survive for 5 years, so it is not identical to the percentage of people actually alive 5 years later. Because the measurement methods and periods differ, it is also not a value to be compared directly with the American numbers.

These numbers are values that group together many people diagnosed at a certain time. One person's future depends on the stage, the subtype, and that person's health status, and this average does not tell you that. Some analyses suggest that non-smokers with lung cancer tend to have longer survival times than smokers, with the caveat that the evidence is still sparse (PMID 30851418).

Drugs Tailored to Genetic Mutations, Drugs That Reawaken Immunity

Lung cancer treatment combines surgery, radiation, and medication based on the type, stage, physical condition, and genetic characteristics of the cancer cells (PMID 41114991). Drug treatment for non-small cell lung cancer is shifting from chemotherapy that attacks cells across the board to treatments tailored to the molecular changes in cancer cells (PMID 26149886).

Targeted therapy is treatment that manages cancer with drugs aiming at specific genetic mutations that have occurred in cancer cells. A representative target is a mutation in a gene called EGFR. In an analysis pooling non-small cell lung cancer patients, this mutation varied greatly by region, being much more common in China than in Europe, and was more common in women, non-smokers, and adenocarcinoma (PMID 27738317). Because it was confirmed that drugs tailored to this mutation work well when it is present, international classification recommends testing for this mutation in advanced adenocarcinoma (PMID 21252716). In lung cancer among non-smokers, these mutations are more common than in people with a history of smoking (EGFR 43% versus 11%), and people with these mutations lived longer when they received targeted therapy than with chemotherapy (PMID 41114991). That does not mean you can guess the mutation from a smoking history. A significant number of people with these mutations had smoked, and not a few non-smokers were found among those with mutations associated with smoking (PMID 24643262).

Immunotherapy is treatment that helps the body's immunity recognize and attack cancer cells again. Immunotherapy is also a branch of non-small cell lung cancer treatment, and palliative care that eases symptoms and protects quality of life is placed at the center of treatment as well (PMID 27188576). However, it is reported that responsiveness to this class of drugs is often low in lung cancer among non-smokers (PMID 41932615). Which treatment is right is decided by the medical team based on the results of testing that person's cancer.

Low-Dose CT Screening — What Did It Reduce?

Screening is a test intended to find disease in advance among people without symptoms. Chest X-rays and sputum tests were tested first as lung cancer screening, but they did not reduce lung cancer deaths (PMID 27130532). Low-dose CT is a chest CT scan adjusted to use less radiation than a standard CT. CT finds small, symptomless lung cancers much better than X-rays (PMID 17941031). However, the mere fact that the survival rate of the cancers found is high is not evidence that screening reduced deaths. Until 2007, observational results showed that the survival rate of cancers found by CT screening was very high, but it had not yet been proven that lung cancer deaths were reduced (PMID 17941031).

The answer came from two large-scale trials that divided groups by a draw, like a lottery. The NLST in the U.S. divided 53,454 people at high risk for lung cancer into two groups between 2002 and 2004, having one group get a low-dose CT once a year for a total of three times, and the other get a chest X-ray the same number of times (PMID 21714641). Participants were current and former smokers aged 55 to 74 (PMID 33687468). Converted to 100,000 people observed for one year, lung cancer deaths were 309 in the X-ray group and 247 in the CT group, a relative reduction of 20.0%. Deaths from all causes combined were also reduced by 6.7% (PMID 21714641).

The NELSON trial in the Netherlands and Belgium followed 13,195 current and former male smokers aged 50 to 74 for over 10 years, dividing them into a group receiving CT screening four times and a group receiving no screening. At year 10, the ratio of lung cancer deaths was 0.76, meaning lung cancer deaths were relatively 24% lower in the screening group (PMID 31995683). Among 2,594 women followed together, the ratio was 0.67, but because the number was small, it was not certain enough to distinguish from chance (PMID 31995683). In an analysis combining 8 low-dose CT trials and 91,122 people, lung cancer deaths were reduced by 21%, and the certainty of the evidence was rated as moderate (PMID 35921047).

20%, 24%, and 21% are all relative magnitudes. The evidence review by the U.S. Preventive Services Task Force (USPSTF) converted this into the number of people, summarizing that in the NLST, one lung cancer death was prevented for every 323 people screened over 6.5 years, and in the NELSON, one was prevented for every 130 people screened over 10 years (PMID 33687468). The lung cancer death ratio for the NLST used in this review was 0.85, a value derived from a different analysis than the 20.0% from the initial 2011 report (PMID 33687468). However, this review considered that trial participants were more likely to benefit in terms of remaining life expectancy than actual screening candidates in the U.S. (PMID 33687468). Why relative magnitudes and the number of people give different impressions is covered in "If the Risk Was Cut in Half, How Many Fewer People Got Sick? — Relative and Absolute Risk".

These results came from people with a heavy smoking history. Pack-years is the value obtained by multiplying the number of packs of cigarettes smoked per day by the number of years smoked. If someone smoked one pack a day for 20 years, or two packs a day for 10 years, that is 20 pack-years (PMID 35921047). In 2021, the USPSTF recommended annual low-dose CT screening for people aged 50 to 80 who have smoked 20 pack-years or more and currently smoke or quit less than 15 years ago (PMID 33687470). The American Cancer Society (ACS) based its criteria on the same age and smoking history in 2023, but did not use the number of years since quitting as a criterion to start or stop screening. This society required having a shared conversation weighing benefits and burdens with a qualified healthcare provider before starting screening, and both guidelines instructed to forgo or stop screening if there are health problems that significantly reduce life expectancy (PMID 33687470, PMID 37909877).

South Korea conducted a pilot project (K-LUCAS) starting in 2017, using the national health screening and public smoking cessation programs as channels, to try low-dose CT screening on people aged 55 to 74 who had smoked for more than 30 pack-years. Among 5,692 participants, 15.2% turned out positive requiring further testing, 0.7% were confirmed with lung cancer, and about two-thirds of the confirmed lung cancers were stage I or II. Complications occurred in 6 people during the diagnostic process, and 1 of them died. The researchers considered this result promising evidence supporting a national screening program that finds early-stage lung cancer and encourages smoking cessation. However, because it was a study observing only people who received screening without a comparison group, whether deaths were reduced could not be measured by this study (PMID 33718017).

Subsequently, South Korea started a national lung cancer screening program using low-dose CT starting in 2019. In a study analyzing data from 2019 to 2023, the subjects were current smokers aged 54 to 74 with 30 pack-years or more, and doctors were required to counsel on screening results and smoking cessation (PMID 41223496). Unlike the U.S. guidelines, people who had quit smoking were not included in the criteria for this period. Criteria can change, so detailed eligibility follows national screening guides.

Screening for people who have never smoked has not yet established a solid evidence base. The USPSTF does not recommend low-dose CT screening for non-smokers, and guidelines differ by country (PMID 41114991). Trials targeting non-smokers are ongoing (PMID 35921047). Among 12,176 non-smokers who received low-dose CT scans at a single institution, 0.45% were diagnosed with lung cancer and 92.7% of those were stage I, but because it was a study looking back only at people who were screened, it is not known whether deaths were reduced (PMID 30445189). There is also a suggestion that some non-smoking groups may have high enough risk for screening to be beneficial (PMID 41932615).

What Screening Causes to Be Paid Together

A false positive is when the test wrongly points to a disease being present when it is not. Of the CT positives during the three rounds of screening in the NLST, 96.4% were false positives (PMID 21714641). For every 1,000 people screened, 17 underwent invasive tests or procedures inside the body because of false-positive results, and fewer than 1 person developed major complications (PMID 33687468).

Overdiagnosis is the act of finding and diagnosing a disease that would have passed without trouble if it had not been found. Among the lung cancers found in low-dose CT screening, the share of overdiagnosis varies widely across studies, from 0% to 67% (PMID 33687468). The pooled estimate from analyses combining trials was 18%, but its range was wide at 0–36%, and the certainty of the evidence was also low (PMID 35921047). In the issue of expanding screening to non-smokers in Asia as well, overdiagnosis and costs are discussed as challenges (PMID 40963259). Beyond that, other abnormalities outside the lung are commonly found incidentally together (4.4% to 40.7% of screened individuals), and rarely, screening radiation can cause cancer (PMID 33687468). There is also a review stating that an incidentally found abnormality can lead to the diagnosis of another treatable disease (PMID 27535387). Anxiety was cited by the USPSTF's evidence review as a burden of screening (PMID 33687468), but in an analysis combining three trials, the anxiety score of the screening group was actually lower, and the certainty of that evidence was low (PMID 35921047). In the Korean pilot program as well, the level of anxiety related to screening was low (PMID 33718017).

This is why screening targets are narrowed to people at high risk. For benefits to outweigh burdens, lung cancer risk must be sufficiently high and remaining life expectancy sufficient. Before age 50, lung cancer is usually too rare for benefits to outweigh burdens and costs, and past age 75, the risk of overdiagnosis can grow rapidly. The same review noted that screening up to age 80 was efficient in terms of lung cancer deaths prevented, but viewed in terms of life span gained compared to overdiagnosis, stopping around age 75 may be more efficient (PMID 33212540).

Low-dose CT screening can reduce lung cancer deaths in people at high risk, but it also brings false positives and the unnecessary tests and procedures that follow, overdiagnosis, incidentally found abnormalities, increased anxiety, and rarely, cancer caused by radiation (PMID 33687468). American College of Chest Physicians (ACCP) guidelines considered that benefits may outweigh burdens in low-dose CT screening, while noting that the scale depends on who is screened, the quality of imaging and interpretation, how findings from screening are handled, and how effective smoking cessation support is (PMID 34270968). The USPSTF graded the net benefit of annual screening in people at high risk as moderate, and the certainty of that judgment as moderate (PMID 33687470).

Scene — When You Hear "A Small Spot Is Visible"

Let us return to the "small spot" that the father in the opening heard about. A pulmonary nodule is a small shadow under 3 centimeters in diameter seen inside the lung on imaging such as a CT scan. Looking at chest CT scans overall, about 30% show a pulmonary nodule, and at least 95% of those are not cancer. They are usually small lumps left by inflammation or lymph nodes inside the lung, and the smaller the nodule, the greater the likelihood that it is not cancer (PMID 35040882). Even in the NLST, which screened people with a high smoking volume, the vast majority of positive CTs were false positives, as we saw earlier (PMID 21714641).

It is difficult to tell what a spot in a single photograph is from the spot alone. The doctor looks at the spot's size and shape, its borders, its location, and whether it has grown compared to previous photos. The person's smoking history and family history, along with signs of infection or inflammation, are also taken into account (PMID 41043896). Guidelines divide when to take the next CT or whether to test further based on the nodule's size and nature, and the person's risk factors (PMID 28240562, PMID 35040882). International guidelines revised in 2017 raised the minimum size of nodules that need separate tracking, and gave the interval for re-imaging as a range rather than a single time point, widening the room to choose according to risk and preferences (PMID 28240562).

Photos taken again over time clear up many things. During the NELSON screening, more than half of the new small nodules that appeared disappeared or became smaller by the next scan. Among the 356 people who had remaining nodules, 7% were diagnosed with lung cancer, and for such nodules, measuring how fast they grew helped single out cancer (PMID 30591535). In the NELSON screening group, 9.2% of people had ambiguous initial readings and had to take a CT one or more additional times, and 2.1% were sent to a specialist for a suspicious nodule (PMID 31995683).

The path handled differs for each spot. Nodules that appear more likely to be cancer go straight to a biopsy or surgery, and those in the middle choose re-imaging, other imaging such as a PET scan, or a biopsy. This review recommends sending nodules that fall on the larger side or clearly grow to a respiratory specialist (PMID 41043896). The USPSTF's evidence review noted that most of the studies it examined did not use modern nodule-reading methods, and that using these methods could reduce false positives and the procedures that follow them (PMID 33687468). In countries where tuberculosis is common, such as South Korea, the marks left by tuberculosis increase the number of positive screening CTs, lowering the rate of correctly identifying people without cancer as negative. There was no difference in the ability to find lung cancer (PMID 32286195).

Most small spots in photographs are not cancer, and what those spots are is figured out by looking at their size, shape, and how they change over time. Which nodules to look at again and when, or whether to test further, is decided by the doctor by putting previous images together with the person's risk factors and preferences (PMID 41043896).

What Changes When You Quit

Preventing lung cancer focuses on not smoking and on quitting cigarettes you already smoke (PMID 32008623). In a study that followed 2,974,820 Koreans aged 30 and older who received National Health Insurance Service health checkups two or more times starting in 2002 for an average of 13.4 years, the lung cancer risk of people who completely quit smoking was 0.58 times that of people who kept smoking (PMID 38319658).

The risk did not drop the moment you quit. The risk of all cancers combined stayed slightly higher for 10 years after quitting compared to people who kept smoking, then came down, and after more than 15 years became half that of people who kept smoking. The lung cancer risk fell 3 years earlier and more steeply than other cancers. The risk fell no matter what age you quit, and lung cancer dropped more the earlier you quit. The lung cancer risk for people who quit before age 50 was 0.43 times that of people who kept smoking, while for those who quit after age 50 it was 0.61 times (PMID 38319658). Because this is a study looking back at past records, these numbers represent an association between quitting and a reduced risk.

Checkups can also serve as an opportunity to recommend quitting (PMID 27535387). American Cancer Society guidelines advise counselors to counsel current smokers to quit and connect them with smoking cessation support (PMID 37909877). A Korean pilot program made smoking cessation counseling mandatory for current smokers, and participation in checkups boosted the motivation to quit (PMID 33718017).

Where to Look Further

Data measuring the burden of screening is still limited, and more trials are needed regarding how much overdiagnosis occurs, who should be screened, how often, until when, and whether to screen people who do not smoke (PMID 35921047).

Why the same test result is interpreted differently depending on the person's initial risk is covered in "What a Test Actually Tells You — An Introduction to Sensitivity, Specificity, and Pretest Probability". The same issue that not everything found is a disease requiring treatment is followed in the thyroid by "What Does the Thyroid Do? — The Letter That Sets the Body's Pace, the Reminder That Grows When It Runs Short" and in the colon by "Why Remove Colon Polyps, and What Do Colorectal Cancer Tests Look For? — A Floor Relaid Every Day, Bumps That Mostly Never Become Cancer".

How the lungs breathe and protect the airways can be found in "How Do We Breathe? — An Upside-Down Tree, and the Leaves Where Air Meets Blood" among the other pieces in this series, another disease where smoking narrows the airways in "What Is COPD? — A Balloon That Won't Empty, and the Breath That Leaves in the First Second", and tuberculosis itself in "What Is Tuberculosis? — The Sleeping Ember, and the Fire That Takes Months to Put Out".

The faint net-like pattern sometimes seen by chance on a screening CT, unrelated to lung cancer — interstitial lung abnormalities — is covered in "What Is Pulmonary Fibrosis? — Thickening Paper Windows, Scars on the Wall Oxygen Crosses".

Source Papers

• "Epidemiology of lung cancer." (2021) — PMID 33911981 — Number one in global cancer incidence and deaths (roughly 2 million diagnoses and 1.8 million deaths), smoking accounts for up to 90%, radon is the second leading cause in developed countries, family history increases risk 1.7-fold, asbestos and air pollution are implicated, and electronic cigarettes are hypothesized to increase risk.
• "Epidemiology of Lung Cancer in Korea: Recent Trends." (2016) — PMID 27064578 — Number one cancer death in Korea, adenocarcinoma has overtaken squamous cell carcinoma as the most frequent, and lung cancer in nonsmokers is estimated to be increasing.
• "Non-small-cell lung cancer." (2015) — PMID 27188576 — Non-small-cell lung cancer accounts for roughly 85% of new diagnoses, smoking is the primary risk with radon and air pollution also playing a role, most are diagnosed at advanced stages with a very poor prognosis due to inadequate screening and delayed symptoms, diagnosis relies on imaging and biopsy, accurate staging determines treatment, and immunotherapy, targeted therapy, and palliative care greatly improve quality of life.
• "Lung Cancer in Nonsmoking Individuals: A Review." (2025) — PMID 41114991 — Nonsmokers (fewer than 100 cigarettes in a lifetime) account for 15% to 20% of lung cancers globally, with 60% to 80% being adenocarcinoma and small cell accounting for less than 10%, presenting with symptoms (wheezing, chest pain, shortness of breath, coughing up blood, metastasis symptoms) or incidental discovery, EGFR mutations at 43% versus 11%, USPSTF does not recommend screening for nonsmokers and guidelines vary by country, treatment combines stage, general condition, and molecular features, and patients with mutations have better survival with targeted therapy than with chemotherapy.
• "Lung cancer: Biology and treatment options." (2015) — PMID 26297204 — Lung cancer has two major histological types (small cell and non-small cell) that differ in how they grow and spread, and treatment depends on the type and stage.
• "International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma." (2011) — PMID 21252716 — Adenocarcinoma is the most common histological type, a classification of non-small-cell lung cancer, and testing is recommended in advanced adenocarcinoma because EGFR mutation is a validated predictive marker for targeted drug response.
• "Epidemiology of Lung Cancer." (2016) — PMID 26667337 — Smoking carries a 5 to 10-fold risk with a dose-response relationship, secondhand smoke increases risk by about 20%, e-cigarette risk is not yet consistently defined, along with radon, asbestos, diesel, ionizing radiation, family history, COPD, and infection.
• "Association between second-hand smoke exposure and lung cancer risk in never-smokers: a systematic review and meta-analysis." (2024) — PMID 39537242 — Overall relative risk of 1.24 for secondhand smoke exposure in never-smokers (82 studies), 1.38 for the workplace, with risk increasing by duration, intensity, and pack-years.
• "Secondhand smoke and lung cancer risk in never-smoking women: A cohort and meta-analysis study." (2026) — PMID 41855613 — Secondhand smoke in never-smoking women, meta-analysis relative risk 1.31 in Asia versus 1.13 in Europe and the US, showing a larger effect in Asia.
• "Systematic review and meta-analysis of residential radon and lung cancer in never-smokers." (2021) — PMID 33536262 — Radon is the largest risk factor for lung cancer in never-smokers globally, and excess relative risk per 100 Bq/m³ of residential radon is positive in both never-smokers and smokers.
• "Lung Cancer in Never Smokers: Genetics, Epidemiology, Environmental Exposures, and Distinct Immune Landscape." (2026) — PMID 41932615 — Never-smokers are omitted from current screening guidelines, incidence is 2.3 times higher in Asian never-smokers, fine particulate matter and lung cancer incidence and mortality are linked in East Asia, some populations may be at a risk level where screening is beneficial, and response to immune checkpoint inhibitors is often low.
• "Lung Cancer Screening and Prevention: Beyond Conventional Strategies in a Rapidly Changing Global Milieu." (2026) — PMID 42166705 — In some East Asian populations (particularly women), never-smokers account for more than 60% of diagnosed lung cancer cases.
• "Characteristics of female lung cancer in Korea: analysis of Korean National Lung Cancer Registry." (2020) — PMID 33145034 — 87.5% of 735 female lung cancer cases in Korean registry data were never-smokers.
• "East meets West: ethnic differences in epidemiology and clinical behaviors of lung cancer between East Asians and Caucasians." (2011) — PMID 21527061 — Smoking is the main cause, but indoor coal combustion, cooking fumes, and infections may play important roles in Asian never-smoking women.
• "Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population." (2023) — PMID 37236969 — Most East Asian lung adenocarcinoma susceptibility variants show no association in European populations.
• "Nonsmall cell lung cancer in never smokers." (2009) — PMID 19532009 — Environmental, genetic, hormonal, and viral factors are associated with non-small-cell lung cancer in never-smokers, but none have definitive evidence.
• "Lung cancer occurrence in never-smokers: an analysis of 13 cohorts and 22 cancer registry studies." (2008) — PMID 18788891 — Results do not match the claim that risk is increasing in never-smokers, with higher incidence and larger variation among East Asian women.
• "Lung Cancer Screening." (2016) — PMID 27535387 — Survival is longer the earlier the stage at diagnosis, NLST shows a 20% reduction, screening is an opportunity to promote smoking cessation, and risks include overdiagnosis, radiation, and false positives.
• "Screening for Lung Cancer: US Preventive Services Task Force Recommendation Statement." (2021) — PMID 33687470 — US lung cancer 5-year survival rate is 20.5%, earlier stages have a better prognosis, annual low-dose CT is recommended for adults aged 50 to 80 years with a 20 pack-year smoking history who currently smoke or have quit within the past 15 years, and screening should be discontinued after 15 years of smoking cessation or when life expectancy is limited.
• "Lung cancer survival among never smokers." (2019) — PMID 30851418 — Never-smokers appear to have longer survival than smokers, but evidence is sparse and further study is needed.
• "Genomic alterations in lung adenocarcinoma." (2015) — PMID 26149886 — Treatment for non-small-cell lung cancer has shifted from cytotoxic chemotherapy to personalized treatment based on molecular changes.
• "The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis." (2016) — PMID 27738317 — EGFR mutation overall is 32.3%, 38.4% in China versus 14.1% in Europe, and higher in women, never-smokers, and adenocarcinoma.
• "Republished: lung cancer in never-smokers. Does smoking history matter in the era of molecular diagnostics and targeted therapy?" (2014) — PMID 24643262 — A significant portion of patients with targetable mutations have a smoking history, and a substantial number of patients with smoking-associated mutations are never-smokers, so smoking status should not be used to screen for mutations.
• "Screening for lung cancer: A systematic review and meta-analysis." (2016) — PMID 27130532 — Chest X-ray (plus or minus sputum cytology) screening does not reduce lung cancer mortality, low-dose CT in high-risk groups reduces mortality, and population-wide implementation requires standardization to reduce harms.
• "Computed tomography screening for lung cancer: review of screening principles and update on current status." (2007) — PMID 17941031 — CT detects small asymptomatic lung cancers much better than X-rays, though mortality reduction was unproven at the time despite high survival rates in single-arm observational studies, along with false positives and overdiagnosis.
• "Reduced lung-cancer mortality with low-dose computed tomographic screening." (2011) — PMID 21714641 — NLST involving 53,454 participants, three rounds of low-dose CT versus X-ray, positive rates of 24.2% versus 6.9% with 96.4% of positives being false positives, lung cancer deaths of 247 versus 309 per 100,000 person-years (a 20.0% relative reduction), and a 6.7% reduction in all-cause mortality.
• "Screening for Lung Cancer With Low-Dose Computed Tomography: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force." (2021) — PMID 33687468 — NLST (ages 55 to 74) and NELSON (ages 50 to 74) in high-risk smokers, number needed to screen of 323 over 6.5 years and 130 over 10 years, false positives leading to 17 invasive procedures and fewer than one major complication per 1,000 people, overdiagnosis of 0% to 67%, incidental findings of 4.4% to 40.7%, increased anxiety and rare radiation-induced cancers, and most studies did not use current nodule evaluation methods.
• "Reduced Lung-Cancer Mortality with Volume CT Screening in a Randomized Trial." (2020) — PMID 31995683 — NELSON trial with 13,195 men, lung cancer deaths of 2.50 versus 3.30 per 1,000 person-years with a 10-year ratio of 0.76, women at 0.67 (95% confidence interval 0.38 to 1.14), additional CT rate of 9.2%, and suspicious nodule referral rate of 2.1%.
• "Impact of low-dose computed tomography (LDCT) screening on lung cancer-related mortality." (2022) — PMID 35921047 — Eight trials with 91,122 participants, 21% reduction in lung cancer mortality (moderate certainty), 18% overdiagnosis (0% to 36%, low certainty), 20 pack-year example, limited harm data, and trials in never-smokers ongoing.
• "Screening for lung cancer: 2023 guideline update from the American Cancer Society." (2024) — PMID 37909877 — Annual screening for adults aged 50 to 80 years with a 20 pack-year or greater smoking history currently or in the past, years since quitting is not a start or stop criterion, shared decision-making, smoking cessation counseling for current smokers, and no screening when life expectancy is limited.
• "Feasibility of implementing a national lung cancer screening program: Interim results from the Korean Lung Cancer Screening Project (K-LUCAS)." (2021) — PMID 33718017 — From 2017 targeting ages 55 to 74 with over 30 pack-years, covering 8.3% of examinees aged 50 and older, among 5,692 participants 15.2% tested positive, 0.7% were confirmed, about two-thirds were early stage, 6 experienced complications (1 death), mandatory smoking cessation counseling for current smokers, and promoting motivation to quit.
• "Role of Low-Dose Computerized Tomography in Lung Cancer Screening among Never-Smokers." (2019) — PMID 30445189 — Single-institution retrospective cohort, 0.45% lung cancer and 92.7% stage I among 12,176 never-smokers, and the value of screening in never-smokers requires further study.
• "Low-Dose Computed Tomography Screening for Lung Cancer in Asia, Including Never-Smokers." (2026) — PMID 40963259 — The proportion of never-smoking women in Asia, along with overdiagnosis and economic constraints, remain challenges.
• "Lung Cancer Screening by Low-Dose Computed Tomography - Part 1: Expected Benefits, Possible Harms, and Criteria for Eligibility and Population Targeting." (2021) — PMID 33212540 — Screening should be for individuals at high risk with sufficient remaining life expectancy, as incidence is generally too low before age 50 and the risk of overdiagnosis rises sharply after age 75.
• "Screening for Lung Cancer: CHEST Guideline and Expert Panel Report." (2021) — PMID 34270968 — The balance of benefits and harms depends on target selection, imaging quality and interpretation, management of detected findings, and smoking cessation intervention effectiveness.
• "Initial Pulmonary Nodule Management for the Generalist: A Brief Review." (2025) — PMID 41043896 — Nodules are focal opacities with an average diameter of 30 mm or less, 8 to 30 mm or clear growth warrants referral to a pulmonologist, found in about one-quarter of CT scans, about 95% are benign, malignancy probability is estimated using patient factors, size, attenuation, margin, location, calcification, and growth compared to prior imaging, low probability warrants serial CT, high probability warrants biopsy or resection, and intermediate probability warrants surveillance, PET, or biopsy.
• "Evaluating the Patient With a Pulmonary Nodule: A Review." (2022) — PMID 35040882 — Nodules found in about 30% of chest CT scans, at least 95% are benign (mostly granulomas or intrapulmonary lymph nodes), smaller size increases the likelihood of being benign, management by size intervals, and treatment based on malignancy probability, test safety, and patient preference.
• "Guidelines for Management of Incidental Pulmonary Nodules Detected on CT Images: From the Fleischner Society 2017." (2017) — PMID 28240562 — Minimum size threshold for routine follow-up raised, and follow-up intervals presented as ranges to reflect risk and preference.
• "Persisting new nodules in incidence rounds of the NELSON CT lung cancer screening study." (2019) — PMID 30591535 — 55% of new solid nodules resolved, 7% of 356 participants with unresolved nodules had lung cancer, and risk was stratified using growth evaluation such as volume doubling time.
• "Lung Cancer CT Screening and Lung-RADS in a Tuberculosis-endemic Country: The Korean Lung Cancer Screening Project (K-LUCAS)." (2020) — PMID 32286195 — Tuberculosis sequelae are associated with false-positive readings but not with lung cancer, specificity drops to 80% from 85%, and sensitivity shows no difference.
• "Lung Cancer 2020: Epidemiology, Etiology, and Prevention." (2020) — PMID 32008623 — Smoking is the main risk factor, so prevention focuses on avoiding smoking and quitting.
• "Cancer Risk Following Smoking Cessation in Korea." (2024) — PMID 38319658 — 2,974,820 Koreans followed for a mean of 13.4 years, lung cancer hazard ratio of 0.58 in complete quitters, overall cancer risk slightly elevated for 10 years after quitting before dropping by half after 15 years or more, lung cancer risk decreased 3 years earlier, quitting before age 50 yielded a hazard ratio of 0.43 versus 0.61 after, and risk decreased at any age.
• "Changes in Uptake, Participant Disparities, and Screening Outcomes of the Korean National Lung Cancer Screening Program: A Five-Year Experience." (2025) — PMID 41223496 — Korean National Lung Cancer Screening Program initiated in 2019, 2019 to 2023 data targeting ages 54 to 74 with a 30 pack-year or greater smoking history, providing screening results and smoking cessation counseling.
• "Recent Trends of Lung Cancer in Korea." (2021) — PMID 33587838 — Korean lung cancer 5-year relative survival increased from 11.3% (1993 to 1995) to 30.2% (2013 to 2017), likely thanks to advances in diagnosis and treatment.
• "Radon." (2010) — PMID 21199598 — Radon is a radioactive gas emitted from uranium-containing soil and rock, accumulating in poorly ventilated enclosed spaces.
• "Health Effects of Radon Exposure." (2019) — PMID 31250572 — Radon is a decay product of uranium and thorium, and the most common cause of lung cancer after smoking.