Lung cancer is a malignant epithelial tumor of the lung that is not a single disease but two biologically and therapeutically distinct entities: non–small cell lung cancer (NSCLC, ~85%) and small cell lung cancer (SCLC, ~15%).^[1][2] The single most important change from legacy teaching is that lung cancer is no longer managed as one disease: histologic subtype, molecular driver status, and PD-L1 expression now dictate therapy in advanced disease, and low-dose CT (LDCT) screening plus stage-shift have begun to bend the mortality curve.^[3][4]

This microchapter covers risk factors and relevant contextual data for lung cancer. Definition, classification, epidemiology, screening, diagnosis, staging, treatment, and prognosis are summarized only as needed for context and are detailed in their dedicated microchapters.

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide — approximately 2.48 million new cases and 1.8 million deaths in 2022, with the global burden projected to rise toward 4.6 million cases and 3.5 million deaths by 2050 absent intervention.^[5][6] In the US it remains the leading cause of cancer death despite falling incidence.^[7] US lung cancer death rates are declining faster than incidence; the ACS reports the 2014–2020 mortality decline accelerated to approximately −5.3%/year in men and −4.3%/year in women, reflecting reduced smoking, earlier-stage diagnosis, and improved therapy.^[8] Detailed demographics and secular trends belong in the Epidemiology microchapter.

Cigarette smoking is the single most important cause of lung cancer, accounting for roughly 80–90% of cases and an ~85% population-attributable fraction in the US, with a 10- to 30-fold (≈20-fold) relative risk versus never-smokers.^[9][10][11] Risk rises with cumulative exposure in a nonlinear dose-response: mean relative risk ≈5.1 at 20 pack-years and ≈13.4 at ~51 pack-years, with diminishing marginal risk beyond ~40 pack-years.^[12] Risk declines with sustained cessation.^[9][12] Cigars, pipes, and bidis also cause lung cancer.^[9]

Living with a person who smokes increases non-smoker risk by ~20–30% and is responsible for an estimated ~3,500 US non-smoker lung cancer deaths annually (~2.7% of US lung cancer cases).^[9][10]

Radon is the second-leading cause overall and the leading environmental cause in never-smokers (~12% of US lung cancers; up to ~21,000 deaths/year).^[13][10] The EPA recommends mitigation at ≥4 pCi/L (150 Bq/m³) and consideration between 2–4 pCi/L.^[10]

Established occupational carcinogens include asbestos, arsenic, chromium, nickel, beryllium, cadmium, silica dust, diesel exhaust, and ionizing radiation; several act independently of and multiplicatively with smoking.^[9][11] Ambient air pollution (PM2.5; IARC group 1) and household solid-fuel/cooking-oil fumes are additional contributors, particularly in never-smoking women.^[13][10]

Family history of lung cancer in a first-degree relative confers an ~2–4× risk. COPD, pulmonary fibrosis, prior thoracic radiotherapy, East Asian female ancestry, and germline variants also increase risk.^[11][13][14] Approximately 15–25% of lung cancers occur in never-smokers, a growing proportion, with higher rates of targetable EGFR and ALK alterations.^[13][15][14]

Annual LDCT screening is recommended for eligible high-risk adults (USPSTF Grade B: age 50–80 years, ≥20 pack-years, currently smoking or quit within 15 years). Eligibility thresholds, Lung-RADS management, and shared decision-making belong in the Screening microchapter.^[4][8]

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Prior to the introduction of cigarette smoking and industrial carcinogens, lung cancer was thought to be a rare disease. Of all the tumors detected on autopsy, lung cancer accounted for only 1% of cancers in the 1800s. The majority of cases of lung cancer were associated with occupational hazards due to radon exposure. The association between lung cancer and smoking was not defined until the mid-20th century.

• The historical data on lung cancer is described below:^{[1][2][3][4][5][6][7][8]}
• The majority of cases of lung cancer were associated with occupational hazards. Death among miners was reported to be caused by Bergkrankheit (mountain sickness).
• During World War 1, cigarette smoking gained popularity because the soldiers used to smoke in trenches to relieve stress, so did the civilians and the women at home. General John J. (“Black Jack”) Pershing reportedly stated: “You ask me what it is we need to win this war. I answer tobacco as much as bullets.”
• In 1924, radon gas was first reported to be a prominent cause of lung cancer among miners.
• In 1929, Fritz Lickint, a German physician, published a paper and suggested that lung cancer patients were likely to be smokers.
• In 1929, Fritz Lickint launched an anti-tobacco campaign in Germany.
• In the 1930s, clinicians started suspecting the association between cigarette smoking and lung cancer due to an increased number of cases.
• The association between lung cancer and smoking was not defined until the mid-20th century. The first reports between lung cancer and smoking were often confounded by gender, given that men were more likely to be smokers compared to women.
• In the 1950s, Doll and Hill in England provided additional corroboration for a causal association between smoking and lung cancer.
• In the 1950s, Cuyler Hammond and Ernest Wynder in the U.S provided additional corroboration for a causal association between smoking and lung cancer.
• In 1961, the first case of adenocarcinoma of the lung was reported.
• The 1969, Springer Handbook of Special Pathology is considered to be the landmark publication that highlighted the role of smoking in the development of lung cancer in over 25 pages.
• In 1969, the first surgeon general warning suggesting cigarette smoking to be a hazard for lung cancer was issued.
• In the 1980s, cisplatin-based chemotherapy emerged and demonstrated modest efficacy in the reduction of tumor related symptoms and the improvement of quality of life.

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Primary lung cancers may be classified into small cell lung cancer (~15%) and non small cell lung cancer (~85%). Non small cell lung cancer are a heterogeneous group of lung cancers that are often grouped together because they share similar clinical features (e.g. prognosis and management). The 2015 WHO histological classification of tumors of the lung categorized lung tumors into malignant epithelial tumors, benign epithelial tumors, lymphoproliferative tumors, miscellaneous tumors, and metastatic tumors.

Primary lung cancers may be classified into two main categories:^[1]

• Small cell lung cancer (~15%)
• Non small cell lung cancer (~85%).

The World Health Organization (WHO) classifies tumors of the lungs as follows:^[1][2]

• Adenocarcinoma is the most common histologic subtype in nonsmoking individuals, accounting for approximately 60%–80% of cases.
• Squamous cell carcinoma represents about 17% of lung cancers in nonsmokers.
• Small cell lung cancer is uncommon in nonsmoking individuals, comprising fewer than 10% of cases.
• Lung cancers in nonsmoking individuals more frequently contain actionable oncogenic alterations.

• EGFR mutations and ALK rearrangements are particularly enriched in tumors from nonsmoking individuals.

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The pathophysiology of lung cancer includes both genetic and environmental factors. Causality of the majority of lung cancer is linked to tobacco usage. Carcinogenic effects of tobacco smoking may result in DNA mis-replication and mutation. Smoking starts a cascade of events that leads to cancer development, even decades after smoking cessation. Besides smokers, patients with the history of prior respiratory tract or gastrointestinal tract cancer comprise a high-risk population. Other environmental factors include radon, asbestos, viral infections, and states of chronic lung inflammation, all of which may predispose to cellular damage and DNA mutations that predispose to the development of lung cancers.

The pathophysiology of lung cancer includes both genetic and environmental factors.^[1][2][3]

• Lung cancer consists of several histological types.
• Main histological types of lung cancer include:
  • Small cell lung cancer
  • Non small cell lung cancer
    • Adenocarcinoma of the lung
    • Squamous cell carcinoma of the lung
    • Large cell carcinoma of the lung
    • Sarcomatoid carcinoma of the lung
• Smoking starts a cascade of events that leads to cancer.

• Lung cancer pathogenesis can be understood with the help of the following hypothesis:

• • 6q23–25 locus has been identified as a susceptibility gene for familial lung cancer.

• • Tumors of organs such as skin, lung and colon are developed through a process called multistep tumorigenesis.
  • As with other epithelial malignancies, lung cancers are believed to arise from preneoplastic or precursor lesions in the respiratory mucosa.
  • Multistep tumorigenesis is the development of tumor through a series of progressive pathologic events such as preneoplastic or precursor lesions with corresponding genetic and epigenetic aberrations.
  • Hyperplasia, squamous metaplasia, squamous dysplasia, and carcinoma in situ (CIS) comprise changes in the large airways that precede or accompany invasive squamous cell carcinoma of the lung.^[4]
  • Multistep tumorigenesis explains pathogenesis of centrally located squamous cell carcinoma of the lung very well but fails to explain the pathogenesis of large cell lung carcinomas, lung adenocarcinomas, and small cell lung cancer.

• • Another theory on the pathogenesis of lung cancer is the accumulation of molecular abnormalities beyond a certain threshold point, rather than the sequence of alterations.
  • There are no known preneoplastic lesions for the most common type of neuroendocrine lung tumors, small cell carcinoma of the lung,
  • Atypical adenomatous hyperplasia (AAH) is the only sequence of morphologic change identified leading to the development of invasive adenocarcinoma of the lung.
• Pathogenesis of lung cancer is thought to be result of both due to stepwise, sequence-specific and multistage molecular pathogenesis and due to accumulation and combination of genetic and epigenetic abnormalities.

• Preneoplastic lung lesions frequently extend throughout the respiratory epithelium, indicating a field effect in which much of the respiratory epithelium has been mutagenized, presumably from exposure to tobacco-related carcinogens.^[5][6][7]
• Epithelial cells lining the entire respiratory tract that have been exposed to smoking show molecular alterations that may signify the onset of lung cancer, a paradigm known as the “airway field of injury”.
• Premalignant airway fields in the molecular pathogenesis of lung cancer:
  • Smoking induces widespread molecular alterations, such as gene expression changes in exposed epithelia throughout the respiratory tract.
  • The airway field of injury can be seen in smokers with or without lung cancer and is highly relevant for the identification of markers for minimally invasive and early detection of lung cancer.
  • The adjacent airway field of carcinoma represents the field in normal appearing airways adjacent to lung tumors.
  • It has been suggested that in this adjacent field of tumor, there is closer molecular genealogy between lung cancers and airways that are in closest proximity to the tumors compared to airways that are more distant from the tumors.
  • The progression of the molecular airway field of injury to preneoplasia and lung malignancy is still not clear.
  • Molecular changes involved in the development of the airway field of injury and changes mediating progression of this field to lung preneoplasia may help the identification of early markers for lung cancer detection and chemoprevention.

• Lung cancer development is initiated by the activation of oncogenes or inactivation of tumor suppressor genes.^[8]
• Mutations in the K-ras proto-oncogene are responsible for 20% to 30% of non-small cell lung cancer cases.^[9][10]
• Chromosomal damage may also result in the loss of heterozygosity, which subsequently leads to the inactivation of tumor suppressor genes.
• Damage to the following chromosomes are particularly common in small cell lung carcinoma:
  • Chromosome 3p
  • Chromosome 5q
  • Chromosome 13q
  • Chromosome 17p
• The TP53 tumor suppressor gene, located on chromosome 17p, is often mutated in lung cancers.^[11]
• Several genetic polymorphisms are associated with lung cancer. These include polymorphisms in genes coding for:^{[12][13][14][15]}
  • Interleukin-1
  • Cytochrome P450
  • Caspase-8, an apoptosis promoter
  • XRCC1, a DNA repair molecule
• Individuals with these polymorphisms are thought to be more likely to develop lung cancer following exposure to carcinogens.

Although genetics play a significant role in the pathogenesis of lung cancer, it is thought that exposure to environmental risk factors plays an equally important role in the development of lung cancer. The main causes of lung cancer include carcinogens (such as those present in tobacco smoke), ionizing radiation, and viral infections. Chronic exposure results in cumulative alterations to the DNA in the tissue lining the bronchi of the lungs (the bronchial epithelium). Irreversible DNA changes following exposure to carcinogens are directly associated with the development of lung cancer.^[16]

• Cigarette smoking is a leading cause of lung cancer.^{[17][18][19][20][21][22][23][24][25][26]}
• Cigarette smoke contains over 60 known carcinogens including radioisotopes from the radon decay sequence, nitrosamine, and benzopyrene.
• Nicotine is thought to reduce the immune response to malignant growths in the exposed tissue. The length of time an individual smokes, as well as the amount, significantly increases the person’s chance of developing lung cancer.
• Among individuals who stopped smoking, the risk of lung cancer steadily decreases as lung tissue repairs itself and as contaminant particles are eliminated from the lungs.
• It is thought that the risk of lung cancer among persons with a history of smoking (even when stopped) is always higher than those who never smoked.

The association of radon gas exposure to lung cancer is described below:^[27][28]

• Radon is a colorless and odorless gas generated by the breakdown of radioactive radium (decay product of uranium) found in the Earth’s crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous.
• Radon exposure is the second major cause of lung cancer following smoking.
• The mechanism of lung damage following radon exposure is not thought to be due to the radon gas itself, but due to the short-lived alpha decay products that cause cellular damage and DNA mutations.

• Asbestos exposure is associated with many lung diseases, including lung cancer.^[29]
• Tiny asbestos fibers released into the air are breathed into the lungs. The fibers become lodged in the lungs and are stuck for an indefinite amount of time. They can eventually lead to scarring and inflammation.

• Viruses known to be associated with the development of lung cancer in animals and humans include:^{[30][31][32][33][34][35]}
  • Human papillomavirus
  • JC virus
  • Simian virus 40 (SV40)
  • BK virus
  • Cytomegalovirus
  • HIV
• These viruses may affect the cell cycle and inhibit apoptosis, allowing uncontrolled cell division.
• HIV has also been thought to increase the risk of developing lung cancer. Although the mechanism is unknown, HIV is thought to be associated with a state of chronic lung inflammation that may potentiate cellular damage and DNA mutations.

• There may be a correlation between general inflammation of lung tissue and the development of lung cancer.^[35]
• Neutrophils are released in response to bacterial infection and are considered to be the initial responders during inflammation.
• The hypothesis is that neutrophils may activate reactive oxygen or nitrogen species, which can bind to DNA and lead to genomic alterations. Accordingly, inflammation may be thought of as an initiator or promoter of lung cancer development. Also, tissue repair from inflammation is associated with cellular proliferation. During cellular proliferation there may be errors in chromosomal replication that can cause further DNA mutation.
• Angiogenesis, a significant process during tumor growth, may be promoted by chronic states of inflammation, which often require increased blood flow to sites of inflammation.

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The direct cause of lung cancer is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumors suppressor genes (e.g. TP53) or both. The risk of these genetic mutations may be increased following exposure to environmental insults.

• The direct cause of lung cancer is DNA mutations that often result in either activation of proto-oncogenes (e.g. K-RAS) or the inactivation of tumors suppressor genes (e.g. TP53) or both.^[1][2]
• The risk of these genetic mutations may be increased following exposure to environmental insults, which are regarded as risk factors that predispose to the development of lung cancer.

• To view a comprehensive list of risk factors that increase the risk of lung cancer, click here.

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Lung cancer must be differentiated from other conditions that cause hemoptysis, cough, dyspnea, wheezing, chest pain, dysphonia, dysphagia, unexplained weight loss, unexplained loss of appetite, and fatigue. These conditions include pneumonia, bronchitis, metastatic cancer from a non-thoracic primary site, infectious granuloma, pulmonary tuberculosis, tracheal tumors, and a thyroid mass.

Lung cancer is the most common cause of cancer-associated mortality and the second most common type of cancer among both genders. Individuals > 50 years of age who have a history of smoking are at increased risk. Historically, the incidence of lung cancer is significantly higher among males compared to females. This increased ratio is thought to be attributed to the increased rates of smoking among men. However, more women are being diagnosed with lung cancer due to the increased rate of smoking among women. In 2014, the incidence of lung cancer in the United States was approximately 70 cases per 100,000. Lung cancer in nonsmoking individuals (defined as <100 lifetime cigarettes) accounts for approximately 15%–20% of all lung cancer cases worldwide, with reported U.S. incidence rates higher in females as compared to males.

• In 2014, the incidence of lung cancer in the US alone was approximately 70 cases per 100,000.^[1]
• Being the most common cancer diagnosed worldwide, it accounted for 2.1 million new cases in 2018.^[2]
• In 2015, the US State Kentucky recorded the highest incidence rate in both men (105.6 per 100,000) and women (77.5 per 100,000) in the country.
• In 2015, the US State Utah recorded the lowest incidence rate in both men (29.6 per 100,000) and women (22.1 per 100,000) in the country.
• Adult cigarette smoking in the United States has declined substantially over the past two decades, accompanied by a parallel reduction in overall lung cancer incidence.
• Lung cancer in nonsmoking individuals (defined as <100 lifetime cigarettes) accounts for 15% to 20% of all lung cancers worldwide.^[3]
• Epidemiologic data from multiple cohorts indicate a rising incidence and proportion of lung cancer among nonsmoking individuals over recent decades (14.4 to 20.8 per 100000 person-years in females and 4.8 to 12.7 per 100000 person-years in males).^[3]

• In the United States, the age-adjusted prevalence of cancer of the lungs and bronchus is estimated to be 100 per 100,000.^[4]
• The prevalence of lung cancer significantly increases among smokers and individuals with chronic exposure to risk factors for lung cancer.

• Being the most common cancer diagnosed worldwide, lung cancer is responsible for 1.8 million deaths in 2018.^[2]

• The American Cancer Society estimates that approximately 142,670 individuals will die of lung cancer in the US in the year 2019.^[5]
• The mortality rate for men is 46.7 per 100,000 individuals.^[6][7]
• The mortality rate for women is 31.9 per 100,000 individuals.^[6][7]

• Lung cancer is more common in older adults. It is rare in people under age of 45 years.
• While the overall age adjusted incidence of cancer of the lungs and bronchus in the United States between 2007 and 2011 is 60 per 100,000, the age-adjusted incidence of lung cancer by age category is:^[4]
  • Under 65 years: 18.1 per 100,000
  • 65 and over: 349.9 per 100,000
  • Lung cancer in nonsmoking individuals is diagnosed at a slightly younger median age (67 years) compared with individuals who have a history of smoking (70 years).

• In the United States, the age-adjusted prevalence of cancer of the lungs and bronchus by race in 2011 was:^[4]
  • Black: 70 – 95 per 100,000
  • White: 50 – 70 per 100,000
  • Asian/Pacific islander: 40 – 50 per 100,000
  • Hispanic: 30 – 40 per 100,000
  • In United States, the age adjusted incidence of lung cancer among nonsmoking women by race during 2000 to 2013 was:
  • Asian: 17.5 per 100,000
  • Non-Hispanic White females: 10.1 per 100,000

• Males are thought to be more predisposed to the development of lung cancer. This gender discrepancy is often attributed to the historically increased rate of smoking among males compared to females.
• The male to female ratio for the incidence of lung cancer is approximately 1.4 to 1.^[4]
• Lung cancer incidence among nonsmoking women has increased substantially over time (0.4 per 100 000 person-years in 1972 to 6.2 per 100 000 person-years in 2015).^[8]
• Lung cancer incidence among nonsmoking men have remained largely stable (6.5 per 100 000 person-years in 1972 vs 6.7 per 100 000 person-years in 2015).^[8]

• The incidence of lung cancer is lower in the developing countries. It is unknown whether this decreased incidence is due to decreased cancer rates or decreased detection rates.^[9]
• Eastern Europe has the highest lung cancer mortality among men.

• Western Europe and the U.S. have the highest incidence of lung cancer and the highest mortality among women.

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The most potent risk factor in the development of lung cancer is tobacco smoking. Other risk factors include second hand smoke, air pollution, family history of lung cancer, radiation therapy to the chest, and exposure to radon, asbestos and other chemical carcinogens.

The following may increase one’s risk of lung cancer:^[1][2][3]

• Smoking
• Second-hand smoke
• Family history of lung cancer
• Air pollution
• Radiation therapy to the chest
• Radon gas exposure
• Asbestos
• High level of arsenic in drinking water
• Occupational exposure to chemical carcinogens
• Previous lung disease
• Indoor burning of coal
• Weakened immune system
• Lupus

Smoking

• Cigarette smoking is the leading cause of lung cancer.^[4][5][6][7]
• Both active and passive smoking are associated with increased risk of lung cancer.
• The risk of lung cancer is associated with increased quantity of cigarette smoking as well as increased duration of smoking.
• There is no evidence that smoking low-tar cigarettes lowers the risk (however lung cancer has occurred in people who have never smoked).
• The more cigarettes you smoke per day and the earlier you started smoking, the greater your risk of lung cancer.
• Recently introduced e-cigarettes, which were thought to be risk-free were recently demonstrated to be also associated with a significantly increased risk of lung cancer due to the presence of formaldehyde.^[8]
• In the United States, smoking is estimated to account for 87% of lung cancer cases (90% in men and 85% in women).^[9]*There is approximately a 20 year lag period between smoking and death due to lung cancer (in men). Shown below is an image depicting the correlation between smoking and lung cancer.

Second-hand Smoke

• Second-hand smoke is what smokers exhale and what rises from a burning cigarette, pipe or cigar. It is also called environmental tobacco smoke (ETS) or involuntary/passive smoking.^[10]

• Second-hand smoke contains the same chemicals as smoke that is actively inhaled.
• Second-hand smoke is a risk factor for lung cancer among non-smokers.
• No amount of exposure to second-hand smoke is safe.^[11]

Air Pollution

• Emissions from automobiles, factories and power plants are thought to pose potential risks.^[12]

• Researchers have shown that individual components of the outdoor air pollution cause cancer. These components include diesel engine exhaust, benzene, particulate matter and some polycyclic aromatic hydrocarbons (PAHs).^[13]

Family History of Lung Cancer^[14]

• Family history of lung cancer may increase the risk of lung cancer.
• First-degree relatives of people who have had lung cancer may have a slightly higher risk of developing lung cancer themselves.
• The increased risk among first-degree relatives could be due to a number of factors, such as shared behaviors or living with the same exposure to carcinogens.
• Studies of families with a strong history of lung cancer have found that the increased risk might be due to a mutation in a lung cancer gene.
• Other studies have shown that the risk of lung cancer in a family increases if a family member developed the disease at an early age.

Radiation Therapy to the Chest

• A history of radiation therapy to the chest increases the risk of lung cancer due to the development of cellular damage and DNA mutations.
• The risk of lung cancer increases for people who have had previous exposure to ionizing radiation.
• People who have been treated with radiation therapy to the chest for cancers such as Hodgkin lymphoma or breast cancer, are at increased risk of developing lung cancer. The risk is further increased in people who smoke.

Radon Exposure

• Radon is a colorless, odorless, and tasteless gas that comes from the natural breakdown of uranium in rocks and soil.

• Radon exposure increases the risk of lung cancer. Radon is the leading cause of lung cancer in non-smokers and the second leading cause of lung cancer in smokers.

• The risk of developing lung cancer depends on how much radon a person is exposed to, how long they are exposed as well as whether or not they smoke. The risk from radon is much higher in people who smoke than in those who don’t.

Asbestos Exposure

• Exposure to asbestos fibers in the air that people breathe increases the risk of lung cancer.

• The risk of asbestos exposure is highest for people who work with asbestos, such as miners or those who work with it in manufacturing.
• Studies have shown that the combination of smoking and asbestos exposure is especially hazardous.

Exposure to Other Chemical Carcinogens

• Arsenic and inorganic arsenic compounds
• Beryllium and beryllium compounds
• Cadmium and cadmium compounds
• Chemicals used in rubber manufacturing, iron and steel founding, and painting
• Chloromethyl ethers and bischloromethylether
• Chromium (VI) compounds
• Cobalt–tungsten carbide
• Diesel engine exhaust
• Mustard gas
• Polycyclic aromatic hydrocarbons (PAHs)
• Radioactive ores, such as uranium and plutonium
• Silica dust and crystalline silica
• Some nickel compounds

• Smoking marijuana
• Indoor burning of wood
• High-temperature frying
• Meat-based diet
• Physical inactivity
• Occupational exposure to certain chemicals
• Removal of both ovaries

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Lung cancer screening is a strategy used to identify early lung cancer in people, before they develop symptoms. Screening refers to the use of medical tests to detect disease in asymptomatic people. Screening studies for lung cancer have only been done in high risk populations, such as smokers and workers with occupational exposure to certain substances. This is because radiation exposure from screening could actually induce carcinogenesis in a small percentage of screened subjects, so this risk should be mitigated by a (relatively) high prevalence of lung cancer in the population being screened. A pulmonary nodule larger than 5 – 6 mm is considered a positive result for screening with x-ray or computed tomography.

About 50% of smokers meet the criteria of 20 pack years^[1].

Uptake of lung cancer screening is low^[2].

As of 2021, screening for lung cancer is not an implemented quality measure nor reportable^[3].

In 2021, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) recommended screening for lung cancer among smokers and former smokers who are between 50 to 80 years old and who have smoked 20 pack years or more and either continue to smoke or have quit smoking within the past 15 years (grade B recommendation).^[4]

MEDICARE requires that screening include counseling for the benefits of screening and smoking cessation^[5].

• In 2013, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) recommended screening for lung cancer among smokers and former smokers who are between 55 to 80 years old and who have smoked 30 pack years or more and either continue to smoke or have quit smoking within the past 15 years (grade B recommendation).^[6]
• The USPSTF guideline was based on a modeling study using data from the National Lung Screening Trial (NLST) and Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) randomized controlled trials . The modeling study did not include the MILD randomized controlled trial that suggested harm.^{[7][8][9][10]}.

• Clinical practice guidelines issued by the American College of Chest Physicians in 2013 recommend:^{[11] [12][13]}
  • For smokers and former smokers who are between the age of 55 to 74 years and who have smoked for 30 pack years or more and either continue to smoke or have quit within the past 15 years, it was suggested that annual screening with low dose computed tomography (LDCT) should be offered in settings that can deliver the comprehensive care provided to the National Lung Screening Trial (NLST) participants.

• In 2004, a clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) gave a grade I recommendation indicating that “the evidence is insufficient to recommend for or against screening asymptomatic persons for lung cancer”.^[14][15]

• In 2007, a clinical practice guideline by American College of Chest Physicians recommended not to screen for lung cancer.^[16]

Lung-RADS version 1.1 by the American College of Radiology guides interpretation of scans.

The Swenson prediction rule can aid prediction^[17].

• Regular chest radiography and sputum examination programs were not effective in reducing mortality from lung cancer.^[18]
• Earlier studies (Mayo Lung Project and Czechoslovakia lung cancer screening study, combining over 17,000 smokers) showed that earlier detection of lung cancer was possible but without any improvement in mortality.
• At present, no professional or specialty organization advocates screening for lung cancer outside of clinical trials.

• A computed tomography (CT) scan can uncover tumors not yet visible on an X-ray.
• CT scanning is now being actively evaluated as a screening tool for lung cancer in high risk patients, and it is showing promising results.
• The USA-based National Cancer Institute is currently completing a randomized trial comparing CT scans with chest radiographs. Several single-institution trials are ongoing around the world.^[19]

• The International Early Lung Cancer Action Project is a cohort study of 31,000 high-risk patients that found benefit from screening.^[20]
  • In this study 85% of the 484 detected lung cancers were stage I and thus highly treatable. Mathematically, these stage I patients would have an expected 10-year survival of 88%. However, there was no randomization of patients (all received CT scans and there was no comparison group receiving only x-rays) and the patients were not actually followed up to 10 years post detection (the median follow up was 40 months).

• A cohort of 3,200 current or former smokers found no benefit. These patients were screened for 4 years and offered 3 or 4 CT scans. Lung cancer diagnoses were 3 times as high, and surgeries were 10 times as high, as predicted by a model, but there were no significant differences between observed and expected numbers of advanced cancers or deaths.^[21]

• The National Lung Screening Trial (NLST) reported reduction in the diagnosis of advanced-stage cancers.^[22]
• The DANTE trial has been inconclusive.^[23]

The cost per year of life save from smoking cessation^[24][25] is less than the costs per year of life saved from screening for lung cancer with low-dose computed tomography^[26][8].

The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease. Patients experience non-specific symptoms such as cough, hemoptysis, dyspnea, chest pain, difficulty speaking, difficulty swallowing, lack of appetite, weight loss, and fatigue from 3 weeks to 3 months before seeking medical attention. There are a variety of complications associated with lung cancer, such as pleural effusion, leg weakness, paresthesias, bladder dysfunction, seizures, hemiplegia, cranial nerve palsies, confusion, personality changes, skeletal pain, pleuritic pain, atelectasis, and bronchopleural fistula. The prognosis of lung cancer is poor if diagnosed at the advanced stages.

• The majority of lung cancers present with advanced disease because the symptoms tend to occur later in the course of the disease.^[1]
• Patients experience non-specific symptoms such as cough, hemoptysis, dyspnea, chest pain, difficulty speaking, difficulty swallowing, lack of appetite, weight loss, and fatigue from 3 weeks to 3 months before seeking medical attention.
• Depending on the duration of the presence of symptoms, the tumor cells may double 20 times.^[1]
• In more advanced disease, the tumor may spread to other organs such as the spinal cord, brain, and bone.
• These patients may develop symptoms such as leg weakness, paresthesias, bladder dysfunction, seizures, hemiplegia, cranial nerve palsies, confusion, personality changes, skeletal pain, and pleuritic pain.^[1]
• Once the cancer spreads to the other organs, it is most likely fatal.
• Most nonsmoking individuals with lung cancer present with advanced disease at diagnosis( unresectable stage III or metastatic stage IV). 10% – 25% have brain metastases at diagnosis, particularly in the presence of certain genomic alterations such as EGFR mutations.

General Complications

The complications associated with lung cancer are:^[2][3]

• Breathing difficulties

• Lung cancer patients can experience trouble in breathing especially when tumors grow and block the airways. Also, it is possible for fluid to build up in the lungs of the patients which can negatively affect breathing.

• Pneumonia

• If the cancer grows in the airway, it may obstruct airflow, causing breathing difficulties. This can lead to accumulation of secretions behind the blockage, predisposing the patient to pneumonia.

• Hemoptysis

• Occasionally, lung cancer can cause bleeding in the airways which can result in hemoptysis.

• Pain

• It is possible that lung cancer will cause pain as well, especially if it spreads to the pleura or other areas of the body, like the bones.

• Pleural effusion

• Lung cancer can cause fluid to build up in the lungs which can cause breathing difficulties.

• Metastasis

• In many cases, lung cancer will spread to other parts of the body. Some of the more common places lung cancer metastasizes to are the bones, liver, brain, and adrenal glands.

• Horner’s syndrome

• Tumors in the apex of the lung, known as Pancoast tumors, may invade locally into the sympathetic nervous system leading to Horner’s syndrome.

• Superior vena cava syndrome
  • SVCS is a group of symptoms caused by obstruction of the superior vena cava. More than 60% of cases of superior vena cava obstruction are caused by malignancies, especially with a tumor outside the vessel compressing the vessel wall.

Surgical Complications

• Bronchopleural fistula

• It is when air leaks from a pneumonectomy bronchial stump.
• Approximately 2% of the patients that undergo a pneumonectomy experience this.
• It will most commonly occur approximately 7 to 10 days after surgery.

• Hemothorax

• Atelectasis
• Sputum retention

The prognosis of lung cancer is poor and it depends on the following factors:

• Whether or not the tumor can be removed by surgery
• Stage of the cancer
• Patient’s general health
• Whether the cancer has just been diagnosed or has recurred

Non-small Cell Lung Cancer Survival Rate by Stage^[4]

Small Cell Lung Cancer Survival Rate

• To view the prognosis among patients with small cell lung carcinoma, please click Here.