Editing Lung cancer

{{Short description|Malignant tumor characterized by uncontrolled cell growth in lung tissue}}
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{{About|lung carcinomas|other lung tumors|Lung tumor}}
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{{Infobox medical condition (new)
| name            = Lung cancer
| synonyms        = Lung carcinoma<ref>{{Cite web |title=Carcinoma, Non-Small-Cell Lung|publisher=National Library of Medicine|url=https://meshb.nlm.nih.gov/record/ui?ui=D002289 |access-date=2025-05-18 |website=meshb.nlm.nih.gov}}</ref>
| image           = LungCACXR.PNG
| caption         = A [[chest X-ray]] showing a tumor in the lung (marked by arrow)
| alt             = X-ray with an arrow pointing to a hazy circular mass in the chest
| field           = [[Oncology]], [[pulmonology]]
| symptoms        = [[Coughing]] (including [[Hemoptysis|coughing up blood]]), [[dyspnea|shortness of breath]], [[chest pain]]
| complications   =
| onset           = After age 40;{{sfn|Horn|Iams|2022|loc="Epidemiology"}} 70 years on average{{sfn|Bade|Dela Cruz|2020|loc="Age"}}
| duration        =
| types           = [[Small-cell lung carcinoma]] (SCLC), [[non-small-cell lung carcinoma]] (NSCLC)
| causes          =
| risks           = {{hlist|[[Tobacco smoking]]|[[Air pollution]]|[[Asbestos]]|[[Radon]]|Other environmental [[mutagen]]s}}
| diagnosis       = [[Medical imaging]], [[tissue biopsy]]
| differential    =
| prevention      = Avoid smoking and other environmental mutagens
| treatment       = [[Surgery]], [[chemotherapy]], [[radiation therapy|radiotherapy]], molecular therapies, [[immune checkpoint inhibitor]]s
| medication      =
| prognosis       = [[Five-year survival rate]]: 10 to 20% (most countries){{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Lung cancer"}}
| frequency       = 2.2&nbsp;million (2020){{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Lung cancer"}}
| deaths          = 1.8&nbsp;million (2020){{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Lung cancer"}}
}}

'''Lung cancer''', also known as '''lung carcinoma''', is a malignant [[tumor]] that begins in the [[lung]]. Lung cancer is caused by [[genetic damage]] to the [[DNA]] of [[cell (biology)|cell]]s in the airways, often caused by [[cigarette smoking]] or inhaling damaging chemicals. Damaged airway cells gain the ability to multiply unchecked, causing the growth of a tumor. Without treatment, tumors spread throughout the lung, damaging lung function. Eventually lung tumors [[metastasize]], spreading to other parts of the body.

Early lung cancer often has no symptoms and can only be detected by [[medical imaging]]. As the cancer progresses, most people experience nonspecific respiratory problems: [[coughing]], [[shortness of breath]], or [[chest pain]]. Other symptoms depend on the location and size of the tumor. Those suspected of having lung cancer typically undergo a series of imaging tests to determine the location and extent of any tumors. Definitive diagnosis of lung cancer requires a [[biopsy]] of the suspected tumor be examined by a [[pathologist]] under a [[microscope]]. In addition to recognizing cancerous cells, a pathologist can classify the tumor according to the type of cells it originates from. Around 15% of cases are [[small-cell lung cancer]] (SCLC), and the remaining 85% (the [[non-small-cell lung cancer]]s or NSCLC) are [[adenocarcinoma]]s, [[squamous-cell carcinoma]]s, and [[large-cell carcinoma]]s. After diagnosis, further imaging and biopsies are done to determine the cancer's [[cancer staging|stage]] based on how far it has spread.

Treatment for early stage lung cancer includes [[surgery]] to remove the tumor, sometimes followed by [[radiation therapy]] and [[chemotherapy]] to kill any remaining cancer cells. Later stage cancer is treated with radiation therapy and chemotherapy alongside drug treatments that target specific cancer subtypes. Even with treatment, only around 20% of people survive five years on from their diagnosis.{{sfn|Rivera|Mody|Weiner|2022|loc="Introduction"}} Survival rates are higher in those diagnosed at an earlier stage, diagnosed at a younger age, and in women compared to men.

Most lung cancer cases are caused by [[tobacco smoking]]. The remainder are caused by exposure to hazardous substances like [[asbestos]] and [[radon]] gas, or by [[genetic mutation]]s that arise by chance. Consequently, lung cancer prevention efforts encourage people to avoid hazardous chemicals and quit smoking. Quitting smoking both reduces one's chance of developing lung cancer and improves treatment outcomes in those already diagnosed with lung cancer.

Lung cancer is the most diagnosed and deadliest cancer worldwide, with 2.2 million cases in 2020 resulting in 1.8 million deaths.{{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Lung cancer"}} Lung cancer is rare in those younger than 40; the average age at diagnosis is 70 years, and the average age at death 72.{{sfn|Bade|Dela Cruz|2020|loc="Age"}} Incidence and outcomes vary widely across the world, depending on patterns of tobacco use. Prior to the advent of cigarette smoking in the 20th century, lung cancer was a rare disease. In the 1950s and 1960s, increasing evidence linked lung cancer and tobacco use, culminating in declarations by most large national health bodies discouraging tobacco use.
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==Signs and symptoms==
Early lung cancer often has no symptoms. When symptoms do arise they are often [[Signs and symptoms#Nonspecific symptoms|nonspecific]] respiratory problems – [[cough]]ing, [[shortness of breath]], or [[chest pain]] – that can differ from person to person.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} Those who experience coughing tend to report either a new cough, or an increase in the frequency or strength of a pre-existing cough.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} Around one in four [[Hemoptysis|cough up blood]], ranging from small streaks in the [[sputum]] to large amounts.{{sfn|Nasim|Sabath|Eapen|2019|loc="Clinical Manifestations"}}{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} Around half of those diagnosed with lung cancer experience shortness of breath, while 25–50% experience a dull, persistent chest pain that remains in the same location over time.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} In addition to respiratory symptoms, some experience [[systemic disease|systemic symptoms]] including [[anorexia (symptom)|loss of appetite]], [[weight loss]], general weakness, [[fever]], and [[night sweats]].{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}}{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}}

Some less common symptoms suggest tumors in particular locations. Tumors in the [[thorax]] can cause breathing problems by obstructing the [[trachea]] or disrupting the nerve to the [[thoracic diaphragm|diaphragm]]; [[dysphagia|difficulty swallowing]] by compressing the [[esophagus]]; [[hoarseness]] by disrupting the [[nerve]]s of the [[larynx]]; and [[Horner's syndrome]] by disrupting the [[sympathetic nervous system]].{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}}{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Horner's syndrome is also common in tumors at the [[Apex of lung|top of the lung]], known as [[Pancoast tumor]]s, which also cause [[shoulder pain]] that radiates down the little-finger side of the arm as well as destruction of the topmost [[rib]]s.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} [[Swollen]] [[lymph node]]s above the [[collarbone]] can indicate a tumor that has spread within the chest.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} Tumors obstructing bloodflow to the heart can cause [[superior vena cava syndrome]] (swelling of the upper body and shortness of breath), while tumors infiltrating the area around the heart can cause [[cardiac tamponade|fluid buildup around the heart]], [[arrhythmia]] (irregular heartbeat), and [[heart failure]].{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}}

About one in three people diagnosed with lung cancer have symptoms caused by [[metastases]] in sites other than the lungs.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Lung cancer can metastasize anywhere in the body, with different symptoms depending on the location. Brain metastases can cause [[headache]], [[nausea]], [[vomiting]], [[seizure]]s, and [[neurological deficit]]s. Bone metastases can cause pain, [[bone fracture]]s, and compression of the [[spinal cord]]. Metastasis into the [[bone marrow]] can [[cytopenia|deplete blood cells]] and cause [[leukoerythroblastosis]] (immature cells in the blood).{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Liver metastases can cause [[hepatomegaly|liver enlargement]], pain in the [[Quadrants and regions of abdomen|right upper quadrant of the abdomen]], fever, and weight loss.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}}

Lung tumors often cause the release of body-altering [[hormone]]s, which cause unusual symptoms, called [[paraneoplastic syndrome]]s.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Inappropriate hormone release can cause dramatic shifts in concentrations of blood [[Mineral (nutrient)|minerals]]. Most common is [[hypercalcemia]] (high blood calcium) caused by over-production of [[parathyroid hormone-related protein]] or [[parathyroid hormone]]. Hypercalcemia can manifest as nausea, vomiting, abdominal pain, constipation, [[polydipsia|increased thirst]], [[polyuria|frequent urination]], and altered mental status.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Those with lung cancer also commonly experience [[hypokalemia]] (low potassium) due to inappropriate secretion of [[adrenocorticotropic hormone]], as well as [[hyponatremia]] (low sodium) due to overproduction of [[antidiuretic hormone]] or [[atrial natriuretic peptide]].{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} About one of three people with lung cancer develop [[nail clubbing]], while up to one in ten experience [[hypertrophic pulmonary osteoarthropathy]] (nail clubbing, joint soreness, and skin thickening). A variety of [[autoimmune disease|autoimmune disorder]]s can arise as paraneoplastic syndromes in those with lung cancer, including [[Lambert–Eaton myasthenic syndrome]] (which causes muscle weakness), [[sensory neuropathies]], [[polymyositis|muscle inflammation]], [[encephalitis|brain swelling]], and autoimmune deterioration of [[cerebellum]], [[limbic system]], or [[brainstem]].{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Up to one in twelve people with lung cancer have paraneoplastic blood clotting, including [[migratory venous thrombophlebitis]], clots in the heart, and [[disseminated intravascular coagulation]] (clots throughout the body).{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}} Paraneoplastic syndromes involving the skin and kidneys are rare, each occurring in up to 1% of those with lung cancer.{{sfn|Horn|Iams|2022|loc="Clinical Manifestations"}}

==Diagnosis==
[[File:Thorax CT peripheres Brronchialcarcinom li OF.jpg|right|thumb|alt=CT scan of lung, with tumor appearing as a sharp white shape|[[CT scan]] showing a cancerous tumor in the left lung]]

A person suspected of having lung cancer will have imaging tests done to evaluate the presence, extent, and location of tumors. First, many [[primary care provider]]s perform a [[chest X-ray]] to look for a mass inside the lung.<ref name=NHS>{{cite web|url=https://www.nhs.uk/conditions/lung-cancer/diagnosis/ |accessdate=30 November 2022 |title=Diagnosis – Lung Cancer |publisher= [[National Health Service]] |date=1 November 2022}}</ref> The X-ray may reveal an obvious mass, the widening of the [[mediastinum]] (suggestive of spread to [[lymph node]]s there), [[atelectasis]] (lung collapse), consolidation ([[pneumonia]]), or [[pleural effusion]];<ref>{{cite web | title=Lung Carcinoma: Tumors of the Lungs | publisher=Merck Manual Professional|edition= online|url=http://www.merck.com/mmpe/sec05/ch062/ch062b.html#sec05-ch062-ch062b-1405 | access-date=21 July 2021 |date=July 2020 }}</ref> however, some lung tumors are not visible by X-ray.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Presentation/Initial Evaluation"}} Next, many undergo [[CT scan|computed tomography (CT) scanning]], which can reveal the sizes and locations of tumors.<ref name=NHS/>{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Noninvasive Staging"}}

A definitive diagnosis of lung cancer requires a [[biopsy]] of the suspected tissue be [[histopathology|histologically]] examined for cancer cells.{{sfn|Horn|Iams|2022|loc="Diagnosing Lung Cancer"}} Given the location of lung cancer tumors, biopsies can often be obtained by minimally invasive techniques: a fiberoptic [[Bronchoscopy|bronchoscope]] that can retrieve tissue (sometimes guided by [[endobronchial ultrasound]]), [[fine needle aspiration]], or other imaging-guided biopsy through the skin.{{sfn|Horn|Iams|2022|loc="Diagnosing Lung Cancer"}} Those who cannot undergo a typical biopsy procedure may instead have a [[liquid biopsy]] taken (that is, a sample of some body fluid) which may contain [[circulating tumor DNA]] that can be detected.{{sfn|Alexander|Kim|Cheng|2020|loc="Liquid Biopsy"}}

[[File:Diagram showing a bronchoscopy CRUK Trim.svg|thumb|alt=Diagram of a machine attached to a tube running down a person's mouth and into their trachea and bronchi|Diagram showing a [[bronchoscopy]]]]
Imaging is also used to assess the extent of cancer spread. [[Positron emission tomography]] (PET) scanning or combined [[PET-CT]] scanning is often used to locate metastases in the body. Since PET scanning is less sensitive in the brain, the [[National Comprehensive Cancer Network]] recommends [[magnetic resonance imaging]] (MRI) – or CT where MRI is unavailable – to scan the brain for metastases in those with NSCLC and large tumors, or tumors that have spread to the nearby lymph nodes.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Suspected Metastatic Disease"}} When imaging suggests the tumor has spread, the suspected metastasis is often biopsied to confirm that it is cancerous.{{sfn|Horn|Iams|2022|loc="Diagnosing Lung Cancer"}} Lung cancer most commonly metastasizes to the brain, bones, liver, and [[adrenal gland]]s.{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Clinical manifestations"}}

Lung cancer can often appear as a [[solitary pulmonary nodule]] on a chest radiograph or CT scan. In lung cancer screening studies as many as 30% of those screened have a lung nodule, the majority of which turn out to be benign.{{sfn|Tanoue|Mazzone|Tanner|2022|loc="Evidence for Lung Cancer Screening"}} Besides lung cancer many other diseases can also give this appearance, including [[hamartoma]]s, and infectious [[granuloma]]s caused by [[tuberculosis]], [[histoplasmosis]], or [[coccidioidomycosis]].{{sfn|Salahuddin|Ost|2023|loc="Table 110-1: Differential Diagnosis of Solitary Pulmonary Nodules"}}

===Classification===
[[File:Lung cancer histology collection.png|thumb|upright=1.4|alt=Microscope images of lung tissue. At top-left, healthy lung with clear air-filled alveoli. Others are full of tumor or material, per caption.|[[H&E stain]]ed samples from lung biopsies: (Top-left) Normal bronchiole surrounded by alveoli, (top-right) adenocarcinoma with papillary (finger-like) growth, (bottom-left) alveoli filled with mucin suggesting adenocarcinoma nearby, (bottom-right) squamous-cell carcinoma, with alveoli full of keratin.]]
[[File:Histopathology of small cell carcinoma, annotated.png|thumb|230px|Histopathology of small-cell carcinoma, with typical findings<ref>Image by Mikael Häggström, MD. Source for findings: {{cite web|url=https://www.pathologyoutlines.com/topic/lungtumorsmallcell.html|title=Lung - Small cell carcinoma|website=Pathology Outlines|author=Caroline I.M. Underwood, M.D., Carolyn Glass, M.D., Ph.D.}} Last author update: 20 September 2022</ref>]]
At diagnosis, lung cancer is classified based on the type of cells the tumor is derived from; tumors derived from different cells progress and respond to treatment differently. There are two main types of lung cancer, categorized by the size and appearance of the malignant cells seen by a [[histopathology|histopathologist]] under a [[microscope]]: [[small cell lung cancer]] (SCLC; 15% of cases) and [[non-small-cell lung cancer]] (NSCLC; 85% of cases).{{sfn|Thai|Solomon|Sequist|Gainor|2021|loc="Histology"}} SCLC tumors are often found near the center of the lungs, in the major airways.{{sfn|Rudin|Brambilla|Faivre-Finn|Sage|2021|loc="Signs and Symptoms"}} Their cells appear small with ill-defined boundaries, not much [[cytoplasm]], many [[mitochondria]], and have distinctive [[cell nucleus|nuclei]] with granular-looking [[chromatin]] and no visible [[nucleoli]].{{sfn|Horn|Iams|2022|loc="Pathology"}} NSCLCs comprise a group of three cancer types: [[adenocarcinoma of the lung|adenocarcinoma]],  [[squamous-cell lung carcinoma|squamous-cell carcinoma]], and [[large-cell lung carcinoma|large-cell carcinoma]].{{sfn|Horn|Iams|2022|loc="Pathology"}} Nearly 40% of lung cancers are adenocarcinomas.{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Precursor lesions"}} Their cells grow in three-dimensional clumps, resemble glandular cells, and may produce [[mucin]].{{sfn|Horn|Iams|2022|loc="Pathology"}} About 30% of lung cancers are squamous-cell carcinomas. They typically occur close to large airways.{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Precursor lesions"}} The tumors consist of sheets of cells, with [[keratinization|layers of keratin]].{{sfn|Horn|Iams|2022|loc="Pathology"}} A hollow cavity and associated [[necrosis|cell death]] are commonly found at the center of the tumor.{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Precursor lesions"}} Less than 10% of lung cancers are large-cell carcinomas,{{sfn|Horn|Iams|2022|loc="Pathology"}} so named because the cells are large, with excess cytoplasm, large nuclei, and conspicuous [[nucleolus|nucleoli]].{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Precursor lesions"}} Around 10% of lung cancers are rarer types.{{sfn|Horn|Iams|2022|loc="Pathology"}} These include mixes of the above subtypes like [[adenosquamous carcinoma]], and rare subtypes such as [[lung carcinoid|carcinoid tumors]], and [[Sarcomatoid carcinoma of the lung|sarcomatoid carcinomas]].{{sfn|Morgensztern|Boffa|Chen|Dhanasopon|2023|loc="Precursor lesions"}}

Several lung cancer types are subclassified based on the growth characteristics of the cancer cells. Adenocarcinomas are classified as lepidic (growing along the surface of intact [[alveoli|alveolar]] walls),{{sfn|Jones|2013|loc="Conclusion"}} [[Acinar adenocarcinoma|acinar]] and [[Papillary adenocarcinoma|papillary]], or micropapillary and solid pattern. Lepidic adenocarcinomas tend to be least aggressive, while micropapillary and solid pattern adenocarcinomas are most aggressive.{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Histology and Prognosis"}}

In addition to examining cell morphology, biopsies are often stained  by [[immunohistochemistry]] to confirm lung cancer classification. SCLCs bear the markers of [[neuroendocrine cell]]s, such as [[chromogranin]], [[synaptophysin]], and [[CD56]].{{sfn|Rudin|Brambilla|Faivre-Finn|Sage|2021|loc="Immunohistochemistry"}} Adenocarcinomas tend to express {{nowrap|[[Napsin-A]]}} and {{nowrap|[[TTF-1]]}}; squamous cell carcinomas lack {{nowrap|Napsin-A}} and {{nowrap|TTF-1}}, but express [[TP63|p63]] and its cancer-specific isoform p40.{{sfn|Horn|Iams|2022|loc="Pathology"}} [[cytokeratin 7|CK7]] and [[cytokeratin 20|CK20]] are also commonly used to differentiate lung cancers. CK20 is found in several cancers, but typically absent from lung cancer. CK7 is present in many lung cancers, but absent from squamous cell carcinomas.{{sfn|Horn|Iams|2022|loc="Immunohistochemistry"}}

===Staging===
{{see also|Lung cancer staging}}
{| class="wikitable floatright" style="text-align:right;font-size:90%;margin-left:1em;background:#E5AFAA;"
|+ Stage group according to TNM classification in lung cancer{{sfn|Lim|Ridge|Nicholson|Mirsadraee|2018|loc="Table 5: Overall stage based on T, N, and M descriptors"}}
|-
! TNM
! Stage group
|-
| T1a N0 M0
| IA1
|-
| T1b N0 M0
| IA2
|-
| T1c N0 M0
| IA3
|-
| T2a N0 M0
| IB
|-
| T2b N0 M0
| IIA
|-
| T1–T2 N1 M0
| rowspan="2" | IIB
|-
| T3 N0 M0
|-
| T1–T2 N2 M0
| rowspan="3" | IIIA
|-
| T3 N1 M0
|-
| T4 N0–N1 M0
|-
| T1–T2 N3 M0
| rowspan="2" | IIIB
|-
| T3–T4 N2 M0
|-
| T3–T4 N3 M0
| IIIC
|-
| Any T, any N, M1a–M1b
| IVA
|-
| Any T, any N, M1c
| IVB
|}

Lung [[cancer staging]] is an assessment of the degree of spread of the cancer from its original source. It is one of the factors affecting both the [[prognosis]] and the treatment of lung cancer.<ref name=ACS-SCLC-Stage>{{cite web|url=https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-sclc.html |accessdate=2 December 2022 |title=Small Cell Lung Cancer Stages |publisher= [[American Cancer Society]] |date=1 October 2019}}</ref>

SCLC is typically staged with a relatively simple system: limited stage or extensive stage. Around a third of people are diagnosed at the limited stage, meaning cancer is confined to one side of the chest, within the scope of a single [[radiotherapy]] field.<ref name=ACS-SCLC-Stage/> The other two thirds are diagnosed at the "extensive stage", with cancer spread to both sides of the chest, or to other parts of the body.<ref name=ACS-SCLC-Stage/>

NSCLC – and sometimes SCLC – is typically staged with the [[American Joint Committee on Cancer]]'s [[TNM staging system|Tumor, Node, Metastasis (TNM) staging system]].<ref name=ACS-NSCLC-Stage>{{cite web|url=https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-nsclc.html |accessdate=2 December 2022 |title=Non-small Cell Lung Cancer Stages |publisher= [[American Cancer Society]] |date=1 October 2019}}</ref> The size and extent of the tumor (T), spread to regional lymph nodes (N), and distant metastases (M) are scored individually, and combined to form stage groups.{{sfn|Horn|Iams|2022|loc="Staging System for Non-Small-Cell Lung Cancer"}}

Relatively small tumors are designated T1, which are subdivided by size: tumors ≤ 1 [[centimeter]] (cm) across are T1a; 1–2 cm T1b; 2–3 cm T1c. Tumors up to 5 cm across, or those that have spread to the [[Pulmonary pleurae|visceral pleura]] (tissue covering the lung) or [[main bronchi]], are designated T2. T2a designates 3–4 cm tumors; T2b 4–5 cm tumors. T3 tumors are up to 7 cm across, have multiple nodules in the same [[Lung#Lobes|lobe]] of the lung, or invade the [[chest wall]], diaphragm (or the [[phrenic nerve|nerve that controls it]]), or area around the heart.{{sfn|Horn|Iams|2022|loc="Staging System for Non-Small-Cell Lung Cancer"}}{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Eight Edition Lung Cancer Stage Classification"}} Tumors that are larger than 7 cm, have nodules spread in different lobes of a lung, or invade the [[mediastinum]] (center of the chest cavity), heart, [[great vessels|largest blood vessels]] that supply the heart, [[trachea]], [[esophagus]], or [[Vertebral column|spine]] are designated T4.{{sfn|Horn|Iams|2022|loc="Staging System for Non-Small-Cell Lung Cancer"}}{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Eight Edition Lung Cancer Stage Classification"}} [[Lymph node]] staging depends on the extent of local spread: with the cancer metastasized to no lymph nodes (N0), pulmonary or [[hilar nodes]] (along the bronchi) on the same side as the tumor (N1), [[Mediastinal lymph node|mediastinal]] or subcarinal lymph nodes (in the middle of the lungs, N2), or lymph nodes on the opposite side of the lung from the tumor (N3).{{sfn|Pastis|Gonzalez|Silvestri|2022|loc="Eight Edition Lung Cancer Stage Classification"}} Metastases are staged as no metastases (M0), nearby metastases (M1a; the space around the lung or the heart, or the opposite lung), a single distant metastasis (M1b), or multiple metastases (M1c).{{sfn|Horn|Iams|2022|loc="Staging System for Non-Small-Cell Lung Cancer"}}

These T, N, and M scores are combined to designate a stage grouping for the cancer. Cancer limited to smaller tumors is designated stage I. Disease with larger tumors or spread to the nearest lymph nodes is stage II. Cancer with the largest tumors or extensive lymph node spread is stage III. Cancer that has metastasized is stage IV. Each stage is further subdivided based on the combination of T, N, and M scores.{{sfn|Horn|Iams|2022|loc="Table 78–6 TNM Stage Groupings, Eighth Edition"}}

{| class="wikitable" style="text-align:center;font-size:90%;margin-left:1em;background:#E5AFAA;"
|+ TNM classification in lung cancer<ref>{{cite web | title=Lung Cancer TNM staging summary|edition=8th | publisher=International Association for the Study of Lung Cancer | url=https://www.iaslc.org/sites/default/files/wysiwyg-assets/iaslc_8th_posters_24x36_2018_final_version_1.pdf | access-date=30 May 2018 | archive-url=https://web.archive.org/web/20180617220133/https://www.iaslc.org/sites/default/files/wysiwyg-assets/iaslc_8th_posters_24x36_2018_final_version_1.pdf | archive-date=17 June 2018 | url-status=dead }}</ref>
|-
|
{| class="wikitable"
|-
! colspan="3" | T: Primary tumor
|-
| T0
| colspan="2" | No primary tumor
|-
| Tis
| colspan="2" | [[Carcinoma in situ]]
|-
| T1
| colspan="2" | Tumor ≤ 3&nbsp;cm across, surrounded by lung or visceral pleura
|-
| rowspan="4" |
| T1mi
| Minimally invasive adenocarcinoma
|-
| T1a
| Tumor ≤ 1&nbsp;cm across
|-
| T1b
| Tumor > 1&nbsp;cm but ≤ 2&nbsp;cm across
|-
| T1c
| Tumor > 2&nbsp;cm but ≤ 3&nbsp;cm across
|-
| rowspan="4" | T2
| rowspan="4" | Any of:
| Tumor size > 3&nbsp;cm but ≤ 5&nbsp;cm across
|-
| Involvement of the main bronchus but not the carina
|-
| Invasion of visceral pleura
|-
| Atelectasis/[[obstructive pneumonitis]] extending to the [[Hilum (anatomy)|hilum]]
|-
| rowspan="2" |
| T2a
| Tumor > 3&nbsp;cm but ≤ 4&nbsp;cm across
|-
| T2b
| Tumor > 4&nbsp;cm but ≤ 5&nbsp;cm across
|-
| rowspan="3" | T3
| rowspan="3" | Any of:
| Tumor size > 5&nbsp;cm but ≤ 7&nbsp;cm across
|-
| Invasion into the chest wall, [[phrenic nerve]], or parietal [[pericardium]]
|-
| Separate tumor nodule in the same lobe
|-
| rowspan="3" | T4
| rowspan="3" | Any of:
| Tumor size > 7&nbsp;cm
|-
| Invasion of the diaphragm, mediastinum, heart, [[great vessels]], [[trachea]], [[Carina of trachea|carina]], [[recurrent laryngeal nerve]], [[esophagus]], or [[vertebral body]]
|-
| Separate tumor nodule in a different lobe of the same lung
|}
| style="vertical-align:top;" |
{| class="wikitable"
|-
! colspan="3" | N: Lymph nodes
|-
| N0
| colspan="2" | No lymph node metastasis
|-
| N1
| colspan="2" | Metastasis to [[ipsilateral]] peribronchial or hilar lymph nodes
|-
| N2
| colspan="2" | Metastasis to ipsilateral mediastinal or subcarinal lymph nodes
|-
| rowspan="2" | N3
| rowspan="2" | Any of:
| Metastasis to scalene or supraclavicular lymph nodes
|-
| Metastasis to contralateral hilar or mediastinal lymph nodes
|}
| style="vertical-align:top;" |
{| class="wikitable"
|-
! colspan="3" | M: Metastasis
|-
| M0
| colspan="2" | No distant metastasis
|-
| rowspan="3" | M1a
| rowspan="3" | Any of:
| Separate tumor nodule in the other lung
|-
| Tumor with pleural or pericardial nodules
|-
| Malignant [[Pleural effusion|pleural]] or [[pericardial effusion]]
|-
| M1b
| colspan="2" | A single metastasis outside the chest
|-
| M1c
| colspan="2" | Two or more metastases outside the chest
|}
|}

===Screening===
{{main|Lung cancer screening}}

Some countries recommend that people who are at a high risk of developing lung cancer be screened at different intervals using low-dose CT lung scans. Screening programs may result in early detection of lung tumors in people who are not yet experiencing symptoms of lung cancer, ideally, early enough that the tumors can be successfully treated and result in decreased mortality.<ref name=Jonas2021>{{Cite web|url=https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/detection.html |accessdate=30 April 2023 |title=Can Lung Cancer Be Found Early? |publisher=American Cancer Society |date=18 January 2023}}</ref> There is evidence that regular low-dose CT scans in people at high risk of developing lung cancer reduces total lung cancer deaths by as much as 20%.{{sfn|Tanoue|Mazzone|Tanner|2022|loc="Evidence for Lung Cancer Screening"}} Despite evidence of benefit in these populations, potential harms of screening include the potential for a person to have a 'false positive' screening result that may lead to unnecessary testing, invasive procedures, and distress.{{sfn|Jonas|Reuland|Reddy|Nagle|2021|loc=Abstract – "Conclusions and Relevance"}} Although rare, there is also a risk of [[radiation-induced cancer]].{{sfn|Jonas|Reuland|Reddy|Nagle|2021|loc=Abstract – "Conclusions and Relevance"}} The [[United States Preventive Services Task Force]] recommends yearly screening using low-dose CT in people between 55 and 80 who have a smoking history of at least 30 [[pack-year]]s.{{sfn|Alexander|Kim|Cheng|2020|loc="Lung Cancer Screening"}} The [[European Commission]] recommends that cancer screening programs across the [[European Union]] be extended to include low-dose CT lung scans for current or previous smokers.{{sfn|Cancer screening in the European Union|2022|p= 27}} Similarly, The Canadian Task Force for Preventative Health recommends that people who are current or former smokers (smoking history of more than 30 pack years) and who are between the ages of 55–74 years be screened for lung cancer.{{sfn|Canadian Task Force|2016|loc= "Recommendations" }}

==Treatment==
{{main|Treatment of lung cancer}}
Treatment for lung cancer depends on the cancer's specific cell type, how far it has [[cancer staging|spread]], and the person's health. Common treatments for early stage cancer includes [[Segmental resection|surgical removal]] of the tumor, [[chemotherapy]], and [[radiation therapy]]. For later-stage cancer, chemotherapy and radiation therapy are combined with newer [[targeted therapy|targeted molecular therapies]] and [[immune checkpoint inhibitor]]s.{{sfn|Rivera|Mody|Weiner|2022|loc="Introduction"}} All lung cancer treatment regimens are combined with lifestyle changes and [[palliative care]] to improve quality of life.{{sfn|Rivera|Mody|Weiner|2022|loc="Palliative Care"}}

===Small-cell lung cancer===
[[File:External beam radiotherapy NCI.jpg|thumb|alt=A person lays on a table under a large machine.|Setup for radiation therapy. The person lies flat while a radiation beam is focused on the tumor site.]]
Limited-stage SCLC is typically treated with a combination of chemotherapy and radiotherapy.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} For chemotherapy, the [[National Comprehensive Cancer Network]] and [[American College of Chest Physicians]] guidelines recommend four to six cycles of a [[Platinum-based antineoplastic|platinum-based chemotherapeutic]] – [[cisplatin]] or [[carboplatin]] – combined with either [[etoposide]] or [[irinotecan]].{{sfn|Rivera|Mody|Weiner|2022|loc="Treatment of Small Cell Lung Cancer"}} This is typically combined with thoracic radiation therapy – 45 [[Gray (unit)|Gray]] (Gy) twice-daily – alongside the first two chemotherapy cycles.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} First-line therapy causes remission in up to 80% of those who receive it; however most people relapse with chemotherapy-resistant disease. Those who relapse are given second-line chemotherapies. [[Topotecan]] and [[lurbinectedin]] are approved by the US [[FDA]] for this purpose.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} Irinotecan, [[paclitaxel]], [[docetaxel]], [[vinorelbine]], etoposide, and [[gemcitabine]] are also sometimes used, and are similarly efficacious.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} [[Prophylactic cranial irradiation]] can reduce the risk of brain metastases and improve survival in those with limited-stage disease.{{sfn|Rudin|Brambilla|Faivre-Finn|Sage|2021|loc="Locally advanced SCLC"}}{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}}

Extensive-stage SCLC is treated first with etoposide along with either cisplatin or carboplatin. Radiotherapy is used only to shrink tumors that are causing particularly severe symptoms. Combining standard chemotherapy with an [[immune checkpoint inhibitor]] can improve survival for a minority of those affected, extending the average person's lifespan by around 2 months.{{sfn|Rudin|Brambilla|Faivre-Finn|Sage|2021|loc="Metastatic Disease"}}

===Non-small-cell lung cancer===
[[File:Lung diagram - tumor surgeries.png|thumb|alt=A lung showing a small tumor. Increasingly large pieces are removed for wedge resection, segmentectomy, and lobectomy respectively|The extent of common surgeries to remove a lung tumor (shown in black). Areas that are surgically removed along with the tumor are shown in blue.]]
<!--Add something about wait-and-see for certain small nodules. A bit in Harrison's-->For stage I and stage II NSCLC the first line of treatment is often surgical removal of the affected lobe of the lung.{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}} For those not well enough to tolerate full lobe removal<!--expand on this?-->, a smaller chunk of lung tissue can be removed by [[wedge resection]] or [[segmentectomy]] surgery.{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}} Those with centrally located tumors and otherwise-healthy respiratory systems may have more extreme surgery to remove an entire lung ([[pneumonectomy]]).{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}} Experienced [[thoracic surgeon]]s, and a high-volume surgery clinic improve chances of survival.{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}} Those who are unable or unwilling to undergo surgery can instead receive radiation therapy. <!--Would be nice to have a clinical recommendation statement here-->[[Stereotactic body radiation therapy]] is best practice, typically administered several times over 1–2 weeks.{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}} Chemotherapy has little effect in those with stage I NSCLC, and may worsen disease outcomes in those with the earliest disease. In those with stage II disease, chemotherapy is usually initiated six to twelve weeks after surgery, with up to four cycles of cisplatin – or [[carboplatin]] in those with kidney problems, [[neuropathy]], or [[hearing impairment]] – combined with [[vinorelbine]], [[pemetrexed]], gemcitabine, or [[docetaxel]].{{sfn|Horn|Iams|2022|loc="Management of Stages I and II NSCLC"}}

Treatment for those with stage III NSCLC depends on the nature of their disease. Those with more limited spread may undergo surgery to have the tumor and affected lymph nodes removed, followed by chemotherapy and potentially radiotherapy. Those with particularly large tumors (T4) and those for whom surgery is impractical are treated with combination chemotherapy and radiotherapy along with the [[immunotherapy]] [[durvalumab]].{{sfn|Horn|Iams|2022|loc="Management of Stage III NSCLC"}} Combined chemotherapy and radiation enhances survival compared to chemotherapy followed by radiation, though the combination therapy comes with harsher side effects.{{sfn|Horn|Iams|2022|loc="Management of Stage III NSCLC"}}

Those with stage IV disease are treated with combinations of pain medication, radiotherapy, immunotherapy, and chemotherapy.{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}} Many cases of advanced disease can be treated with targeted therapies depending on the genetic makeup of the cancerous cells. Up to 30% of tumors have mutations in the ''[[Epidermal growth factor receptor|EGFR]]'' gene that result in an overactive EGFR protein;{{sfn|Alexander|Kim|Cheng|2020|loc="Basis of Molecularly Targeted Therapy in Lung Cancer"}} these can be treated with EGFR inhibitors [[osimertinib]], [[erlotinib]], [[gefitinib]], [[afatinib]], or [[dacomitinib]] – with osimertinib known to be superior to erlotinib and gefitinib, and all superior to chemotherapy alone.{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}} Up to 7% of those with NSCLC harbor mutations that result in hyperactive [[anaplastic lymphoma kinase|ALK]] protein, which can be treated with [[ALK inhibitor]]s [[crizotinib]], or its successors [[alectinib]], [[brigatinib]], and [[ceritinib]].{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}} Those treated with ALK inhibitors who relapse can then be treated with the third-generation ALK inhibitor [[lorlatinib]].{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}} Up to 5% with NSCLC have overactive [[C-Met|MET]], which can be inhibited with [[c-Met inhibitor|MET inhibitors]] [[capmatinib]] or [[tepotinib]].{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}} Targeted therapies are also available for some cancers with rare mutations. Cancers with hyperactive [[BRAF (gene)|BRAF]] (around 2% of NSCLC) can be treated by [[dabrafenib]] combined with the [[MEK inhibitor]] [[trametinib]]; those with activated [[ROS1]] (around 1% of NSCLC) can be inhibited by crizotinib, lorlatinib, or [[entrectinib]]; overactive [[NTRK]] (<1% of NSCLC) by entrectinib or [[larotrectinib]]; active [[RET proto-oncogene|RET]] (around 1% of NSCLC) by [[selpercatinib]].{{sfn|Horn|Iams|2022|loc="Management of Metastatic NSCLC"}}

People whose NSCLC is not targetable by current molecular therapies instead can be treated with combination chemotherapy plus immune checkpoint inhibitors, which prevent cancer cells from inactivating immune [[T cell]]s. The chemotherapeutic agent of choice depends on the NSCLC subtype: cisplatin plus gemcitabine for squamous cell carcinoma, cisplatin plus pemetrexed for non-squamous cell carcinoma.{{sfn|Horn|Iams|2022|loc="Cytotoxic Chemotherapy for Metastatic or Recurrent NSCLC"}} Immune checkpoint inhibitors are most effective against tumors that express the protein [[PD-L1]], but are sometimes effective in those that do not.{{sfn|Horn|Iams|2022|loc="Immunotherapy"}} Treatment with [[pembrolizumab]], [[atezolizumab]], or combination [[nivolumab]] plus [[ipilimumab]] are all superior to chemotherapy alone against tumors expressing PD-L1.{{sfn|Horn|Iams|2022|loc="Immunotherapy"}} Those who relapse on the above are treated with second-line chemotherapeutics [[docetaxel]] and [[ramucirumab]].{{sfn|Horn|Iams|2022|loc="Second-Line Therapy and Beyond"}}

===Palliative care===
[[File:Diagram showing how you have internal radiotherapy for lung cancer CRUK 160.svg|thumb|alt=A machine attached to a tube that goes into a person's mouth and into a bronchus. At the end, an object emits radiation at a lung tumor.|right|[[Brachytherapy]] (internal radiotherapy) for lung cancer given via the airway]]
Integrating palliative care (medical care focused on improving symptoms and lessening discomfort) into lung cancer treatment from the time of diagnosis improves the survival time and quality of life of those with lung cancer.{{sfn|Aragon|2020|loc="Integrating palliative care into lung cancer care"}} Particularly common symptoms of lung cancer are shortness of breath and pain. Supplemental oxygen, improved airflow, re-orienting an affected person in bed, and low-dose [[morphine]] can all improve shortness of breath.{{sfn|Aragon|2020|loc="Dyspnea"}} In around 20 to 30% of those with lung cancer – particularly those with late-stage disease – growth of the tumor can [[airway obstruction|narrow or block the airway]], causing coughing and difficulty breathing.{{sfn|Obeng|Folch|Fernando Santacruz|2018|loc="Introduction", "Prevalence", and "Clinical presentation"}} Obstructing tumors can be surgically removed where possible, though typically those with airway obstruction are not well enough for surgery. In such cases the American College of Chest Physicians recommends opening the airway by inserting a [[stent]], attempting to shrink the tumor with localized radiation ([[brachytherapy]]), or physically removing the blocking tissue by bronchoscopy, sometimes aided by thermal or [[Laser ablation#Medicine|laser ablation]].{{sfn|Obeng|Folch|Fernando Santacruz|2018|loc="Management"}} Other causes of lung cancer-associated shortness of breath can be treated directly, such as [[antibiotic]]s for a lung infection, [[diuretic]]s for [[pulmonary edema]], [[benzodiazepine]]s for anxiety, and [[steroid]]s for airway obstruction.{{sfn|Aragon|2020|loc="Dyspnea"}}

Up to 92% of those with lung cancer report pain, either from tissue damage at the tumor site(s) or nerve damage.{{sfn|Aragon|2020|loc="Cancer-related pain"}} The [[World Health Organization]] (WHO) has developed a three-tiered system for managing cancer pain. For those with mild pain (tier one), the WHO recommends [[acetominophen]] or a [[nonsteroidal anti-inflammatory drug]].{{sfn|Aragon|2020|loc="Cancer-related pain"}} Around a third of people experience moderate (tier two) or severe (tier three) pain, for which the WHO recommends opioid painkillers.{{sfn|Aragon|2020|loc="Cancer-related pain"}} Opioids are typically effective at easing [[nociceptive pain]] (pain caused by damage to various body tissues). Opioids are occasionally effective at easing [[neuropathic pain]] (pain caused by nerve damage). Neuropathic agents such as [[anticonvulsant]]s, [[tricyclic antidepressant]]s, and [[serotonin–norepinephrine reuptake inhibitor]]s, are often used to ease neuropathic pain, either alone or in combination with opioids.{{sfn|Aragon|2020|loc="Cancer-related pain"}} In many cases, targeted radiotherapy can be used to shrink tumors, reducing pain and other symptoms caused by tumor growth.{{sfn|Spencer|Parrish|Barton|Henry|2018|loc="What are the indications for using palliative radiotherapy?"}}

Individuals who have advanced disease and are approaching end-of-life can benefit from dedicated [[end-of-life care]] to manage symptoms and ease suffering. As in earlier disease, pain and difficulty breathing are common, and can be managed with opioid pain medications, transitioning from oral medication to injected medication if the affected individual loses the ability to swallow.{{sfn|Lim|2016|loc="Key area three: providing symptom management in the last days"}} Coughing is also common, and can be managed with opioids or [[cough suppressant]]s. Some experience terminal delirium – confused behavior, unexplained movements, or a reversal of the sleep-wake cycle – which can be managed by antipsychotic drugs, low-dose sedatives, and investigating other causes of discomfort such as [[hypoglycemia|low blood sugar]], [[constipation]], and [[sepsis]].{{sfn|Lim|2016|loc="Key area three: providing symptom management in the last days"}} In the last few days of life, many develop [[terminal secretions]] – pooled fluid in the airways that can cause a rattling sound while breathing. This is thought not to cause respiratory problems, but can distress family members and caregivers. Terminal secretions can be reduced by [[anticholinergic medication]]s.{{sfn|Lim|2016|loc="Key area three: providing symptom management in the last days"}} Even those who are non-communicative or have reduced consciousness may be able to experience cancer-related pain, so pain medications are typically continued until the time of death.{{sfn|Lim|2016|loc="Key area three: providing symptom management in the last days"}}

==Prognosis==
[[File:SEER Lung cancer 5-year survival 2022.pdf|thumb|upright=1.5|alt=Graph showing five-year survival from lung cancer increasing from 1975 (11.7% of people) to 2015 (25.2%).|Percent of people who survive five years from a lung cancer diagnosis over time, according to the [[Surveillance, Epidemiology, and End Results|NIH SEER]] program]]

{| class="wikitable floatright" style="text-align:center;font-size:90%;width:25%;margin-left:1em"
|+ style="background:#E5AFAA;"|Five-year survival in those diagnosed with lung cancer, by stage{{sfn|Goldstraw|Chansky|Crowley|Rami-Porta|2016|loc="Figure 2"}}
|- style="background: #E5AFAA;text-align:center;font-size:90%;"
! abbr="Type" | Clinical stage
!Five-year survival (%)
|-
| IA1
| 92
|-
|IA2
|83
|-
|IA3
|77
|-
| IB
| 68
|-
| IIA
| 60
|-
| IIB
| 53
|-
| IIIA
| 36
|-
| IIIB
| 26
|-
|IIIC
|13
|-
| IVA
| 10
|-
|IVB
|0
|}

Around 19% of people diagnosed with lung cancer survive [[Five-year survival rate|five years from diagnosis]], though prognosis varies based on the stage of the disease at diagnosis and the type of lung cancer.{{sfn|Rivera|Mody|Weiner|2022|loc="Introduction"}} Prognosis is better for people with lung cancer diagnosed at an earlier stage; those diagnosed at the earliest TNM stage, IA1 (small tumor, no spread), have a two-year survival of 97% and five-year survival of 92%.{{sfn|Goldstraw|Chansky|Crowley|Rami-Porta|2016|loc="Figure 2"}} Those diagnosed at the most-advanced stage, IVB, have a two-year survival of 10% and a five-year survival of 0%.{{sfn|Goldstraw|Chansky|Crowley|Rami-Porta|2016|loc="Figure 2"}} Five-year survival is higher in women (22%) than men (16%).{{sfn|Rivera|Mody|Weiner|2022|loc="Introduction"}} Women tend to be diagnosed with less-advanced disease, and have better outcomes than men diagnosed at the same stage.{{sfn|Rivera|Mody|Weiner|2022|loc="Prognostic and Predictive Factors in Lung Cancer"}} Average five-year survival also varies across the world, with particularly high five-year survival in Japan (33%), and five-year survival above 20% in 12 other countries: Mauritius, Canada, the US, China, South Korea, Taiwan, Israel, Latvia, Iceland, Sweden, Austria, and Switzerland.{{sfn|Allemani|Matsuda|Di Carlo|Harewood|2018|loc="Lung"}}

SCLC is particularly aggressive. 10–15% of people survive five years after a SCLC diagnosis.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} As with other types of lung cancer, the extent of disease at diagnosis also influences prognosis. The average person diagnosed with limited-stage SCLC survives 12–20 months from diagnosis; with extensive-stage SCLC around 12 months.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} While SCLC often responds initially to treatment, most people eventually relapse with chemotherapy-resistant cancer, surviving an average 3–4 months from the time of relapse.{{sfn|Horn|Iams|2022|loc="Treatment – Small-Cell Lung Cancer"}} Those with limited stage SCLC that go into complete remission after chemotherapy and radiotherapy have a 50% chance of brain metastases developing within the next two years – a chance reduced by prophylactic cranial irradiation.{{sfn|Rivera|Mody|Weiner|2022|loc="Treatment of Small Cell Lung Cancer"}}

Several other personal and disease factors are associated with improved outcomes. Those diagnosed at a younger age tend to have better outcomes. Those who smoke or experience weight loss as a symptom tend to have worse outcomes. Tumor mutations in [[KRAS]] are associated with reduced survival.{{sfn|Rivera|Mody|Weiner|2022|loc="Prognostic and Predictive Factors in Lung Cancer"}}

===Experience===
The uncertainty of lung cancer prognosis often causes stress, and makes future planning difficult, for those with lung cancer and their families.{{sfn|Temel|Petrillo|Greer|2022|loc="Coping with Prognostic Uncertainty"}} Those whose cancer goes into remission often experience fear of their cancer returning or progressing, associated with poor quality of life, negative mood, and functional impairment. This fear is exacerbated by frequent or prolonged surveillance imaging, and other reminders of cancer risks.{{sfn|Temel|Petrillo|Greer|2022|loc="Coping with Prognostic Uncertainty"}}

==Causes==

Lung cancer is caused by [[genetic damage]] to the [[DNA]] of lung cells. In general, this damage causes loss of function of [[tumor suppressor gene]]s, or gain in function of [[oncogene]]s.{{sfn|Horn|Iams|2022|loc="Molecular Pathology"}} These changes are sometimes random, but are typically induced by breathing in toxic substances such as cigarette smoke.<ref>{{cite web|url=https://www.cancer.org/cancer/lung-cancer/causes-risks-prevention/what-causes.html |title=What Causes Lung Cancer |publisher=American Cancer Society |date=1 October 2019 |accessdate=31 January 2023}}</ref><ref>{{cite web|url=https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/basics/what-causes-lung-cancer |accessdate=31 January 2023 |title=What Causes Lung Cancer? |publisher=American Lung Association |date=17 November 2022}}</ref> Cancer-causing genetic changes affect the [[Cell biology|cell's normal functions]], including [[cell proliferation]], programmed cell death ([[apoptosis]]), and [[DNA repair]].{{sfn|Massion|Lehman|2022|loc=Table 73.1: Hallmarks of Cancer}} Eventually, cells gain enough genetic changes to grow uncontrollably,{{Verify source|date=May 2025}} forming a tumor, and eventually spreading within and then beyond the lung.<!--Cite--> Rampant tumor growth and spread causes the symptoms of lung cancer. If unstopped, the spreading tumor will eventually cause the death of affected individuals.<!--Cite-->

===Smoking===
[[File:Lung Cancer Incidece vers Cigarette Consumption.svg|thumb|upright=1.3|alt=Graph showing that lung cancer rates rise and fall with cigarette consumption. |Relationship between cigarette consumption per person (blue) and male lung cancer rates (dark yellow) in the US]]

[[Tobacco smoking]] is by far the major contributor to lung cancer, causing 80% to 90% of cases.{{sfn|Schabath|Cote|2019|loc="Introduction"}} Lung cancer risk increases with quantity of cigarettes consumed.{{sfn|Bade|Dela Cruz|2020|loc="Tobacco Smoke Carcinogens"}} Tobacco smoking's carcinogenic effect is due to [[List of cigarette smoke carcinogens|various chemicals in tobacco smoke]] that cause DNA mutations, increasing the chance of cells becoming cancerous.<ref>{{cite web|url=https://www.cdc.gov/cancer/tobacco/index.htm |accessdate=29 December 2022 |title=Tobacco and Cancer |date=18 November 2021 |publisher= [[Centers for Disease Control and Prevention]]}}</ref> The [[International Agency for Research on Cancer]] identifies at least 50 chemicals in tobacco smoke as [[carcinogen]]ic, and the most potent is [[tobacco-specific nitrosamines]].{{sfn|Bade|Dela Cruz|2020|loc="Tobacco Smoke Carcinogens"}} Exposure to these chemicals causes several kinds of DNA damage: [[DNA adduct]]s, [[oxidative stress]], and breaks in the DNA strands.{{sfn|Massion|Lehman|2022|loc="DNA Damage Response"}} Being around tobacco smoke – called [[passive smoking]] – can also cause lung cancer. Living with a tobacco smoker increases one's risk of developing lung cancer by 24%. An estimated 17% of lung cancer cases in those who do not smoke are caused by high levels of environmental tobacco smoke.{{sfn|Bade|Dela Cruz|2020|loc="Environmental Tobacco Smoke"}}

[[electronic cigarette|Vaping]] may be a risk factor for lung cancer, but less than that of cigarettes, and further research as of 2021 is necessary due to the length of time it can take for lung cancer to develop following an exposure to carcinogens.{{sfn|Bracken-Clarke|Kapoor|Baird|Buchanan|2021|loc=Abstract – "Conclusion"}}

The smoking of non-tobacco products is not known to be associated with lung cancer development. Marijuana smoking does not seem to independently cause lung cancer – despite the relatively high levels of [[Tar (tobacco residue)|tar]] and known carcinogens in marijuana smoke. The relationship between smoking cocaine and developing lung cancer has not been studied as of 2020.{{sfn|Bade|Dela Cruz|2020|loc="Marijuana and Other Recreational Drugs"}}

===Environmental exposures===
[[File:Bauer Elementary (ASBESTOS-2).JPG|thumb|alt=A sign reads "Danger, asbestos, cancer and lung disease hazard, authorized personnel only" |Sign warning of potential for asbestos exposure, typically used during demolition/renovation of asbestos-containing buildings]]
Exposure to a variety of other toxic chemicals – typically encountered in certain occupations – is associated with an increased risk of lung cancer.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} Occupational exposures to carcinogens cause 9–15% of lung cancer.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} A prominent example is [[asbestos]], which causes lung cancer either directly or indirectly by inflaming the lung.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} Exposure to all commercially available forms of asbestos increases cancer risk, and cancer risk increases with time of exposure.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} Asbestos and cigarette smoking increase risk synergistically – that is, the risk of someone who smokes and has asbestos exposure dying from lung cancer is much higher than would be expected from adding the two risks together.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} Similarly, exposure to [[radon]], a naturally occurring breakdown product of the Earth's [[radioactive element]]s, is associated with increased lung cancer risk. Radon levels vary with geography.{{sfn|Schabath|Cote|2019|loc="Radon"}} Underground miners have the greatest exposure; however even the lower levels of radon that seep into residential spaces can increase occupants' risk of lung cancer. Like asbestos, cigarette smoking and radon exposure increase risk synergistically.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}} Radon exposure is responsible for between 3% and 14% of lung cancer cases.{{sfn|Schabath|Cote|2019|loc="Radon"}}

Several other chemicals encountered in various occupations are also associated with increased lung cancer risk including [[arsenic]] used in [[wood preservation]], [[pesticide]] application, and some ore [[smelting]]; [[ionizing radiation]] encountered during [[uranium mining]]; [[vinyl chloride]] in [[papermaking]]; [[beryllium]] in [[jeweler]]s, [[ceramic]]s workers, missile technicians, and [[nuclear reactor]] workers; [[chromium]] in [[stainless steel]] production, [[welding]], and [[Tanning (leather)|hide tanning]]; [[nickel]] in [[electroplate]]rs, glass workers, metal workers, welders, and those who make batteries, ceramics, and jewelry; and [[diesel exhaust]] encountered by miners.{{sfn|Christiani|Amos|2022|loc="Occupational Exposures"}}

Exposure to [[air pollution]], especially [[particulate matter]] released by motor vehicle exhaust and [[fossil fuel]]-burning power plants, increases the risk of lung cancer.{{sfn|Christiani|Amos|2022|loc="Air Pollution"}}{{sfn|Balmes|Holm|2022|loc=Table 102.2: Major Pollutants Associated with Adverse Pulmonary Effects}} [[Indoor air pollution]] from burning [[Wood fuel|wood]], [[Charcoal-burning|charcoal]], or crop residue for cooking and heating has also been linked to an increased risk of developing lung cancer.{{sfn|Bade|Dela Cruz|2020|loc="Biomass Burning"}} The International Agency for Research on Cancer has classified emission from household burning of coal and biomass as "carcinogenic" and "probably carcinogenic" respectively.{{sfn|Bade|Dela Cruz|2020|loc="Biomass Burning"}}

===Other diseases===
Several other diseases that cause inflammation of the lung increase one's risk of lung cancer. This association is strongest for [[chronic obstructive pulmonary disorder]] – the risk is highest in those with the most inflammation, and reduced in those whose inflammation is treated with [[inhaled corticosteroid]]s.{{sfn|Bade|Dela Cruz|2020|loc="Chronic Lung Diseases"}} Other inflammatory lung and immune system diseases such as [[alpha-1 antitrypsin deficiency]], [[interstitial lung disease|interstitial fibrosis]], [[scleroderma]], ''[[Chlamydia pneumoniae]]'' infection, [[tuberculosis]], and [[HIV infection]] are associated with increased risk of developing lung cancer.{{sfn|Bade|Dela Cruz|2020|loc="Chronic Lung Diseases"}} [[Epstein–Barr virus]] is associated with the development of the rare lung cancer [[lymphoepithelioma-like carcinoma]] in people from Asia, but not in people from [[Western world|Western nations]].{{sfn|Bade|Dela Cruz|2020|loc="Infections"}} A role for several other infectious agents – namely [[human papillomavirus]]es, [[BK virus]], [[JC virus]], [[human cytomegalovirus]], [[SV40]], [[measles virus]], and [[Torque teno virus]] – in lung cancer development has been studied but remains inconclusive as of 2020.{{sfn|Bade|Dela Cruz|2020|loc="Infections"}}

===Genetics===
Particular gene combinations may make some people more susceptible to lung cancer. Close family members of those with lung cancer have around twice the risk of developing lung cancer as an average person, even after controlling for occupational exposure and smoking habits.{{sfn|Christiani|Amos|2022|loc="Genetic Susceptibility to Lung Cancer"}} [[Genome-wide association studies]] have identified many gene variants associated with lung cancer risk, each of which contributes a small risk increase.{{sfn|Bade|Dela Cruz|2020|loc="Genetic Predisposition and History of Cancer"}} Many of these genes participate in pathways known to be involved in carcinogenesis, namely [[DNA repair]], [[inflammation]], the [[cell division cycle]], [[cellular stress response]]s, and [[chromatin remodeling]].{{sfn|Bade|Dela Cruz|2020|loc="Genetic Predisposition and History of Cancer"}} Some rare genetic disorders that increase the risk of various cancers also increase the risk of lung cancer, namely [[retinoblastoma]] and [[Li–Fraumeni syndrome]].{{sfn|Christiani|Amos|2022|loc="High-Risk Syndromes Conferring an Increased Risk of Lung Cancer"}}

==Pathogenesis==
As with all cancers, lung cancer is triggered by mutations that allow tumor cells to endlessly multiply, stimulate [[angiogenesis|blood vessel growth]], avoid [[apoptosis]] (programmed cell death), generate pro-growth signalling molecules, ignore anti-growth signalling molecules, and eventually spread into surrounding tissue or metastasize throughout the body.{{sfn|Horn|Iams|2022|loc="Molecular Pathogenesis"}} Different tumors can acquire these abilities through different mutations, though generally cancer-contributing mutations activate [[oncogene]]s and inactivate [[tumor suppressor]]s.{{sfn|Horn|Iams|2022|loc="Molecular Pathogenesis"}} Some mutations – called "driver mutations" – are particularly common in adenocarcinomas, and contribute disproportionately to tumor development. These typically occur in the [[receptor tyrosine kinase]]s EGFR, BRAF, MET, [[KRAS]], and [[PIK3CA]].{{sfn|Horn|Iams|2022|loc="Molecular Pathogenesis"}} Similarly, some adenocarcinomas are driven by chromosomal rearrangements that result in overexpression of [[Tyrosine kinase|tyrosine kinases]] ALK, ROS1, NTRK, and RET. A given tumor will typically have just one driver mutation.{{sfn|Horn|Iams|2022|loc="Molecular Pathogenesis"}} In contrast, SCLCs rarely have these driver mutations, and instead often have mutations that have inactivated the tumor suppressors [[p53]] and [[Retinoblastoma protein|RB]].{{sfn|Rudin|Brambilla|Faivre-Finn|Sage|2021|loc="Mechanisms/Pathophysiology"}} A cluster of tumor suppressor genes on the short arm of [[chromosome 3]] are often lost early in the development of all lung cancers.{{sfn|Horn|Iams|2022|loc="Molecular Pathogenesis"}}

==Prevention==
===Smoking cessation===
Those who smoke can reduce their lung cancer risk by quitting smoking – the risk reduction is greater the longer a person goes without smoking.{{sfn|Horn|Iams|2022|loc="Risk Factors"}} Self-help programs tend to have little influence on success of smoking cessation, whereas combined counseling and pharmacotherapy improve cessation rates.{{sfn|Horn|Iams|2022|loc="Risk Factors"}} The US FDA has approved [[antidepressant]] therapies and the nicotine replacement [[varenicline]] as first-line therapies to aid in smoking cessation. [[Clonidine]] and [[nortriptyline]] are recommended second-line therapies<!--recommended by whom?-->.{{sfn|Horn|Iams|2022|loc="Risk Factors"}} The majority of those diagnosed with lung cancer attempt to quit smoking; around half succeed.{{sfn|Jassem|2019|loc="Prevalence and determinants of continued tobacco use after diagnosis of cancer"}} Even after lung cancer diagnosis, smoking cessation improves treatment outcomes, reducing cancer treatment toxicity and failure rates, and lengthening survival time.{{sfn|Jassem|2019|loc="Consequences of continued smoking after diagnosis of cancer"}}
{{Multiple image|total_width=300
|image2=Belgian cigarette pack (generic).jpg
|caption2=[[Plain tobacco packaging]] in Belgium labelled "open wound following lung surgery"	
|alt2=A cigarette package features warning text and a large photograph of a person with a large side wound.
|image1=RTD, No Smoking on Platform sign, FCS.jpg
|caption1=No smoking sign at a train station in Colorado
|alt1=A sign reads "No smoking on platform"
}}
At a societal level, smoking cessation can be promoted by [[tobacco control]] policies that make tobacco products more difficult to obtain or use. Many such policies are mandated or recommended by the [[WHO Framework Convention on Tobacco Control]], ratified by 182 countries, representing over 90% of the world's population.{{sfn|Peruga|López|Martinez|Fernández|2021|loc="2.1. Galvanizing global political will around international law"}} The WHO groups these policies into six intervention categories, each of which has been shown to be effective in reducing the cost of tobacco-induced disease burden on a population: 
#increasing the price of tobacco by raising taxes;
#banning tobacco use in public places to reduce exposure;
# banning tobacco advertisements;
#publicizing the dangers of tobacco products;
# instituting help programs for those attempting to quit smoking; and
# monitoring population-level tobacco use and the effectiveness of tobacco control policies.{{sfn|Peruga|López|Martinez|Fernández|2021|loc="2.2. Quadrupling the number of people benefiting from at least one cost-effective tobacco control policy since 2007"}} 
Policies implementing each intervention are associated with decreases in tobacco smoking prevalence. The more policies implemented, the greater the reduction.{{sfn|Arnott|Lindorff|Goddard|2022|p=427}} Reducing access to tobacco for adolescents is particularly effective at decreasing uptake of habitual smoking, and adolescent demand for tobacco products is particularly sensitive to increases in cost.{{sfn|Christiani|Amos|2022|loc="Smoking Behavior and Risk for Lung Cancer"}}

===Diet and lifestyle===

Several foods and dietary supplements have been associated with lung cancer risk. High consumption of some animal products – [[red meat]] (but not other meats or fish), [[saturated fat]]s, as well as [[nitrosamine]]s and [[nitrite]]s (found in salted and smoked meats) – is associated with an increased risk of developing lung cancer.{{sfn|Bade|Dela Cruz|2020|loc="Diet"}} In contrast, high consumption of fruits and vegetables is associated with a reduced risk of lung cancer, particularly consumption of [[cruciferous vegetables]] and raw fruits and vegetables.{{sfn|Bade|Dela Cruz|2020|loc="Diet"}} Based on the beneficial effects of fruits and vegetables, supplementation of several individual vitamins have been studied. Supplementation with [[vitamin A]] or [[beta-carotene]] had no effect on lung cancer, and instead slightly increased mortality.{{sfn|Bade|Dela Cruz|2020|loc="Diet"}} Dietary supplementation with [[vitamin E]] or [[retinoid]]s similarly had no effect.{{sfn|Bade|Dela Cruz|2020|loc="Chemopreventive Agents"}} Consumption of [[polyunsaturated fat]]s, tea, alcoholic beverages, and coffee are all associated with reduced risk of developing lung cancer.{{sfn|Bade|Dela Cruz|2020|loc="Diet"}}

Along with diet, body weight and exercise habits are also associated with lung cancer risk. Being [[overweight]] is associated with a lower risk of developing lung cancer, possibly due to the tendency of those who smoke cigarettes to have a lower body weight.{{sfn|Bade|Dela Cruz|2020|loc="Obesity and Exercise"}} However, being [[underweight]] is also associated with a reduced lung cancer risk.{{sfn|Bade|Dela Cruz|2020|loc="Obesity and Exercise"}} Some studies have shown those who exercise regularly or have better cardiovascular fitness to have a lower risk of developing lung cancer.{{sfn|Bade|Dela Cruz|2020|loc="Obesity and Exercise"}}

==Epidemiology==
[[File:Lung cancer incidence 2020.png|thumb|upright=1.5|alt=World map with countries in one of five colors |[[Age adjustment|Age-standardized]] lung cancer incidence in 2020 per 100,000 people:<ref>{{cite web|url=https://gco.iarc.fr/today/online-analysis-map?v=2020&mode=population&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=15&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=10&group_cancer=1&include_nmsc=0&include_nmsc_other=0&projection=natural-earth&color_palette=default&map_scale=quantile&map_nb_colors=5&continent=0&show_ranking=0&rotate=%255B10%252C0%255D |accessdate=28 April 2023 |title=Estimated age-standardized incidence rates (World) in 2020, lung, both sexes, all ages |publisher=World Health Organization, International Agency for Research on Cancer}}</ref> {{Div col|small=yes|colwidth=10em}}{{legend|#045a8d|>40}}{{legend|#2b8cbe|30–40}}{{legend|#74a9cf|20–30}}{{legend|#bdc9e1|10–20}}{{legend|#f1eef6|<10}}{{div col end}}]]
Worldwide, lung cancer is the most diagnosed type of cancer, and the leading cause of cancer death.{{sfn|Schabath|Cote|2019|loc="Descriptive Epidemiology"}}{{sfn|Christiani|Amos|2022|loc="Introduction"}} In 2020, 2.2&nbsp;million new cases were diagnosed, and 1.8&nbsp;million people died from lung cancer, representing 18% of all cancer deaths.{{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Lung cancer"}} Lung cancer deaths are expected to rise globally to nearly 3 million annual deaths by 2035, due to high rates of tobacco use and aging populations.{{sfn|Christiani|Amos|2022|loc="Introduction"}} Lung cancer is rare among those younger than 40; after that, cancer rates increase with age, stabilizing around age 80.{{sfn|Horn|Iams|2022|loc="Epidemiology"}} The median age of a person diagnosed with lung cancer is 70; the median age of death is 72.{{sfn|Bade|Dela Cruz|2020|loc="Age"}}

Lung cancer incidence varies by geography and sex, with the highest rates in Micronesia, Polynesia, Europe, Asia, and North America; and lowest rates in Africa and Central America.{{sfn|Sung|Ferlay|Siegel|Laversanne|2021|loc="Figure 9"}} Globally, around 8% of men and 6% of women develop lung cancer in their lifetimes.{{sfn|Horn|Iams|2022|loc="Epidemiology"}} The ratio of lung cancer cases in men to women varies considerably by geography, from as high as nearly 12:1 in Belarus, to 1:1 in Brazil, likely due to differences in smoking patterns.{{sfn|Christiani|Amos|2022|loc="Geographic, Gender, and Ethnic Variability"}}

Lung cancer risk is influenced by environmental exposure, namely cigarette smoking, as well as occupational risks in mining, shipbuilding, petroleum refining, and occupations that involve asbestos exposure.{{sfn|Christiani|Amos|2022|loc="Geographic, Gender, and Ethnic Variability"}} People who have smoked cigarettes account for 85–90% of lung cancer cases, and 15% of smokers develop lung cancer.{{sfn|Christiani|Amos|2022|loc="Geographic, Gender, and Ethnic Variability"}} Non-smokers' risk of developing lung cancer is also influenced by tobacco smoking; [[secondhand smoke]] (that is, being around tobacco smoke) increases risk of developing lung cancer around 30%, with risk correlated to duration of exposure.{{sfn|Christiani|Amos|2022|loc="Geographic, Gender, and Ethnic Variability"}} As the global incidence of lung cancer decreases in parallel with declining smoking rates in developed countries, the incidence of lung cancer in individuals who have never smoked is stable or increasing.<ref>{{Cite journal |last1=LoPiccolo |first1=Jaclyn |last2=Gusev |first2=Alexander |last3=Christiani |first3=David C. |last4=Jänne |first4=Pasi A. |date=January 9, 2024 |title=Lung cancer in patients who have never smoked — an emerging disease |journal=Nature Reviews Clinical Oncology |language=en |volume=21 |issue=2 |pages=121–146 |doi=10.1038/s41571-023-00844-0 |issn=1759-4782 |pmc=11014425 |pmid=38195910}}</ref>

==History==
Lung cancer was uncommon before the advent of cigarette smoking. Surgeon [[Alton Ochsner]] recalled that as a [[Washington University School of Medicine|Washington University]] medical student in 1919, his entire medical school class was summoned to witness an autopsy of a man who had died from lung cancer, and told they may never see such a case again.{{sfn|Spiro|Silvestri|2005|loc="Introduction"}}<!--Spiro says the year was 1910, but that must be a mistake as Ochsner would've been 14 years old at the time-->{{sfn|Blum|1999|p=102}} In [[Isaac Adler (physician)|Isaac Adler]]'s 1912 ''Primary Malignant Growths of the Lungs and Bronchi'', he called lung cancer "among the rarest forms of disease";{{sfn|Adler|1912|p=3}} Adler tabulated the 374 cases of lung cancer that had been published to that time, concluding the disease was increasing in incidence.{{sfn|Proctor|2012|loc="Introduction"}} By the 1920s, several theories had been put forward linking the increase in lung cancer to various chemical exposures that had increased including tobacco smoke, asphalt dust, industrial air pollution, and poisonous gasses from World War I.{{sfn|Proctor|2012|loc="Introduction"}}

Over the following decades, growing scientific evidence linked lung cancer to cigarette consumption. Through the 1940s and early 1950s, several [[case-control studies]] showed that those with lung cancer were more likely to have smoked cigarettes compared to those without lung cancer.{{sfn|Proctor|2012|loc="Population studies"}} These were followed by several [[prospective cohort studies]] in the 1950s – including the first report of the [[British Doctors Study]] in 1954 – all of which showed that those who smoked tobacco were at dramatically increased risk of developing lung cancer.{{sfn|Proctor|2012|loc="Population studies"}}
[[File:A Frank Statement.png|thumb|alt=Full page text advertisement |"[[A Frank Statement|A Frank Statement to Cigarette Smokers]]", an advertisement run in newspapers nationwide in January 1954 as part of Hill & Knowlton's campaign to cast doubt on the link between cigarettes and cancer]]
A 1953 study showing that tar from cigarette smoke could cause tumors in mice attracted attention in the popular press, with features in ''[[Life (magazine)|Life]]'' and ''[[Time (magazine)|Time]]'' magazines. Facing public concern and falling stock prices, the [[CEO]]s of six of the largest American tobacco companies gathered in December 1953.{{sfn|Proctor|2012|loc="Animal experimentation"}} They enlisted the help of public relations firm [[Hill+Knowlton Strategies|Hill & Knowlton]] to craft a multi-pronged strategy aiming to distract from accumulating evidence by funding tobacco-friendly research, declaring the link to lung cancer "controversial", and demanding ever-more research to settle this purported controversy.{{sfn|Proctor|2012|loc="Animal experimentation"}}{{sfn|Brandt|2012|loc="Industry response to emerging tobacco science"}} At the same time, internal research at the major tobacco companies supported the link between tobacco and lung cancer; though these results were kept secret from the public.{{sfn|Proctor|2012|loc="Cancer-causing chemicals in cigarette smoke"}}

As evidence linking tobacco use with lung cancer mounted, various health bodies announced official positions linking the two. In 1962, the United Kingdom's [[Royal College of Physicians]] officially concluded that cigarette smoking causes lung cancer, prompting the [[Surgeon General of the United States|United States Surgeon General]] to empanel (enroll or enlist) an advisory committee, which deliberated in secret over nine sessions between November 1962 and December 1963.{{sfn|Hall|2022|loc="Establishing the advisory committee to the US Surgeon General"}} [[Smoking and Health|The committee's report]], published in January 1964, firmly concluded that cigarette smoking "far outweighs all other factors" in causing lung cancer.{{sfn|Hall|2022|loc="Cigarette smoking and lung cancer"}} The report received substantial coverage in the popular press, and is widely seen as a turning point for public recognition that tobacco smoking causes lung cancer.{{sfn|Hall|2022|loc="Establishing the advisory committee to the US Surgeon General"}}{{sfn|Parascandola|2020|loc="Introduction"}}

The connection with [[radon]] gas was first recognized among miners in Germany's [[Ore Mountains]]. As early as 1500, miners were noted to develop a deadly disease called "mountain sickness" ("Bergkrankheit"), identified as lung cancer by the late 19th century.{{sfn|Witschi|2001|p=2}}{{sfn|Mc Laughlin|2012|loc="Miner epidemiological studies"}} By 1938, up to 80% of miners in affected regions died from the disease.{{sfn|Witschi|2001|p=2}} In the 1950s radon and its breakdown products became established as causes of lung cancer in miners. Based largely on studies of miners, the International Agency for Research on Cancer classified radon as "carcinogenic to humans" in 1988.{{sfn|Mc Laughlin|2012|loc="Miner epidemiological studies"}} In 1956, a study revealed radon in Swedish residences. Over the following decades, high radon concentrations were found in residences across the world; by the 1980s many countries had established national radon programs to catalog and mitigate residential radon.{{sfn|Mc Laughlin|2012|loc="Residential radon epidemiology"}}

The first successful [[pneumonectomy]] for lung cancer was performed in 1933 by [[Evarts Graham]] at [[Barnes-Jewish Hospital|Barnes Hospital]] in St. Louis, Missouri.{{sfn|Horn|Johnson|2008|loc="Introduction"}} Over the following decades, surgical development focused on sparing as much healthy lung tissue as possible, with the [[lobectomy]] surpassing the pneumectomy in frequency by the 1960s, and the wedge resection appearing in the early 1970s.{{sfn|Walcott-Sapp|Sukumar|2016|loc="Evolution of Indications and Operative Technique"}}{{sfn|Spiro|Silvestri|2005|loc="Surgery"}} This trend continued with the development of [[video-assisted thoracoscopic surgery]] in the 1980s, now widely performed for many lung cancer surgeries.{{sfn|Walcott-Sapp|Sukumar|2016|loc="A Delayed Entrance to the Modern Era of Minimally Invasive Lung Resection"}}

==Research==

While lung cancer is the deadliest type of cancer, it receives the third-most funding from the US [[National Cancer Institute]] (NCI, the world's largest cancer research funder) behind [[brain cancer]]s and [[breast cancer]].<ref>{{cite web|url=https://www.cancer.gov/about-nci/budget/fact-book/data/research-funding |accessdate=22 April 2023 |title=Funding for Research Areas |date=10 May 2022 |publisher=National Cancer Institute}}</ref> Despite high levels of gross research funding, lung cancer funding per death lags behind many other cancers, with around $3,200 spent on lung cancer research in 2022 per US death, considerably lower than that for brain cancer ($22,000 per death), breast cancer ($14,000 per death), and cancer as a whole ($11,000 per death).<ref>{{cite web|url=https://report.nih.gov/funding/categorical-spending#/ |accessdate=30 April 2023 |title=Estimates of Funding for Various Research, Condition, and Disease Categories (RCDC) |date=31 March 2023 |publisher=US [[National Institutes of Health]]}}</ref> A similar trend holds for private [[nonprofit organization]]s. Annual revenues of lung cancer-focused nonprofits rank fifth among cancer types, but lung cancer nonprofits have lower revenue than would be expected for the number of lung cancer cases, deaths, and potential years of life lost.{{sfn|Kamath|Kircher|Benson|2019|loc="Results"}}

Despite this, many investigational lung cancer treatments are undergoing [[clinical trial]]s – with nearly 2,250 active clinical trials registered as of 2021.{{sfn|Batra|Pawar|Bahl|2021|loc="Practice Points"}} Of these, a large plurality are testing radiotherapy regimens (26% of trials) and surgical techniques (22%). Many others are testing targeted anticancer drugs, with targets including EGFR (17% of trials), [[microtubule]]s (12%), VEGF (12%), immune pathways (10%), mTOR (1%), and [[histone deacetylase]]s (<1%).{{sfn|Batra|Pawar|Bahl|2021|loc="Figure 2: Types of treatment for lung cancer in clinical trials, Phase I-IV"}}

== References ==
{{Reflist}}

===Cited===
{{refbegin|32em}}
'''Books'''
* {{Cite book | vauthors = Adler I | year=1912 | title=Primary Malignant Growths of the Lungs and Bronchi | place= New York | publisher=Longmans, Green, and Company | oclc=14783544 | ol=24396062M }}
* {{cite book |title= Murray & Nadel's Textbook of Respiratory Medicine|edition=7th |date=2022 |publisher=Elsevier |veditors= Broaddus C, Ernst JD, King TE, ''et al''|isbn=978-0323655873|ref=none}}
**{{cite book|vauthors=Balmes JR, Holm SM |chapter=Indoor and Outdoor Air Pollution |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7th |date=2022 |publisher=Elsevier |pages=1423–1434 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
** {{cite book |vauthors=Christiani DC, Amos CI |chapter=Lung Cancer: Epidemiology |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7th |date=2022 |publisher=Elsevier |pages=1018–1028 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
** {{cite book|vauthors=Massion PP, Lehman JM |chapter=Lung Cancer: Molecular Biology and Targets |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7th |date=2022 |publisher=Elsevier |pages=1005–1017 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
** {{cite book|vauthors=Pastis NJ, Gonzalez AV, Silvestri GA |chapter=Lung Cancer: Diagnosis and Staging |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7th |date=2022 |publisher=Elsevier |pages=1039–1051 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
** {{cite book|vauthors=Rivera P, Mody GN, Weiner AA |chapter=Lung Cancer: Treatment |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7 |date=2022 |publisher=Elsevier |pages=1052–1065 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
** {{cite book|vauthors=Tanoue L, Mazzone PJ, Tanner NT |chapter=Lung Cancer: Screening |title=Murray & Nadel's Textbook of Respiratory Medicine |edition=7th |date=2022 |publisher=Elsevier |pages=1029–1038 |veditors= Broaddus C, Ernst JD, King TE, ''et al''}}
* {{Cite book |url=https://data.europa.eu/doi/10.2777/867180 |title=Cancer screening in the European Union |date=2022 |publisher=Publications Office of the European Union |isbn=978-92-76-45603-2 |doi=10.2777/867180 |ref={{harvid|Cancer screening in the European Union|2022}} |author1=European Commission. Directorate General for Research and Innovation. |author2=European Commission Group of Chief Scientific Advisors. }}
* {{cite book|vauthors=Horn L, Iams WT |chapter=78: Neoplasms of the Lung |title=[[Harrison's Principles of Internal Medicine]] |edition=21st |publisher=McGraw Hill |date=2022|veditors= Loscalzo J, Fauci A, Kasper D, ''et al'' |isbn= 978-1264268504}}
* {{cite book|veditors=Bast RC, Byrd JC, Croce CM, ''et al'' |title=Holland-Frei Cancer Medicine |edition=10th |isbn=978-1-119-75068-0 |date=April 2023 |publisher=Wiley |chapter=80: Cancer of the Lung |vauthors=Morgensztern D, Boffa D, Chen A, Dhanasopon A, Goldberg SB, Decker RH, Devarakonda S, Ko JP, Solis Soto LM, Waqar SN, Wistuba II, Herbst RS}}
* {{cite book|vauthors=Salahuddin M, Ost DE |chapter=110: Approach to the Patient with Pulmonary Nodules |publisher=McGraw Hill |title=Fishman's Pulmonary Diseases and Disorders |edition=6th |veditors=Grippi MA, Antin-Ozerkis DE, Dela Cruz CS, ''et al''|isbn=978-1260473988 |year=2023}}

'''Journal articles'''
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* {{cite journal |vauthors=Aragon KN |title=Palliative Care in Lung Cancer |journal=Clin Chest Med |volume=41 |issue=2 |pages=281–293 |date=June 2020 |pmid=32402363 |doi=10.1016/j.ccm.2020.02.005 |s2cid=218633948 }}
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* {{cite journal | vauthors=Batra H, Pawar S, Bahl D | title=Current clinical trials and patent update on lung cancer: a retrospective review | journal=Lung Cancer Management | volume=10 | issue=5 | pages=LMT45 | date=February 2021 | pmid=34084211 | pmc=8162165 | doi=10.2217/lmt-2020-0029 }}
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* {{cite journal | vauthors = Bracken-Clarke D, Kapoor D, Baird AM, Buchanan PJ, Gately K, Cuffe S, Finn SP | title = Vaping and lung cancer – A review of current data and recommendations | journal = Lung Cancer | volume = 153 | pages = 11–20 | date = March 2021 | pmid = 33429159 | doi = 10.1016/j.lungcan.2020.12.030 | s2cid = 231586192 | doi-access =  }}
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* {{cite journal | vauthors = Horn L, Johnson DH | title = Evarts A. Graham and the first pneumonectomy for lung cancer | journal = Journal of Clinical Oncology | volume = 26 | issue = 19 | pages = 3268–3275 | date = July 2008 | pmid = 18591561 | doi = 10.1200/JCO.2008.16.8260 | url = http://jco.ascopubs.org/cgi/pdf_extract/26/19/3268 | access-date = 20 March 2009 | archive-date = 17 March 2020 | archive-url = https://web.archive.org/web/20200317080747/https://ascopubs.org/cgi/pdf_extract/26/19/3268 | url-status = dead }}
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* {{cite journal | vauthors=Lim W, Ridge CA, Nicholson AG, Mirsadraee S | title=The 8th lung cancer TNM classification and clinical staging system: review of the changes and clinical implications | journal=Quantitative Imaging in Medicine and Surgery | volume=8 | issue=7 | pages=709–718 | date =August 2018 | pmc=6127520 | pmid=30211037 | doi=10.21037/qims.2018.08.02 | doi-access=free }}
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{{refend}}

== External links ==
{{commons category|Cancers of bronchus and lung}}
{{wikiquote}}

{{Medical resources
|DiseasesDB = 7616
|ICD11 = {{ICD11|2C24}}, {{ICD11|2C25}}
|ICD10 = {{ICD10|C33}}, {{ICD10|C34}}
|ICD9 = {{ICD9|162}}
|ICDO =
|OMIM =211980
|MedlinePlus = 007194
|eMedicineSubj = med
|eMedicineTopic = 1333
|eMedicine_mult = {{eMedicine2|med|1336}} {{eMedicine2|emerg|335}} {{eMedicine2|radio|807}} {{eMedicine2|radio|405}} {{eMedicine2|radio|406}}
|MeshID = D002283
}}
{{Respiratory tract neoplasia}}
{{Authority control}}

{{DEFAULTSORT:Lung cancer}}
[[Category:Lung cancer| ]]
[[Category:Health effects of tobacco]]
[[Category:Types of cancer]]