Non-small cell lung cancer

aka NSCLC, lung cancer, lung adenocarcinoma, lung squamous cell carcinoma, large cell lung carcinoma

The cancer that kills more people than any other, and the reason most PET scanners are busy. Most cases are found once the disease has already spread, and a scan with radioactive sugar is what decides who can still be cured by surgery.

Non-small cell lung cancer is the group of lung carcinomas that are not small-cell: adenocarcinoma (about 40% of all lung cancers), squamous cell carcinoma (about 25%) and large cell carcinoma (about 10%), classified by the World Health Organization together with the International Association for the Study of Lung Cancer, with adenosquamous, sarcomatoid and salivary gland-type tumours making up the remainder. Squamous tumours usually start near a central bronchus, adenocarcinomas peripherally. Smoking is the dominant cause: on average a smoker's risk is tenfold that of a lifetime non-smoker, and radon, asbestos, air pollution, prior radiation, family history and HIV infection add to it. Subsets of adenocarcinoma carry targetable alterations in EGFR, ALK, ROS1, BRAF, RET, NTRK1-3, MET, KRAS and HER2; EGFR and ALK predominate in never-smokers while KRAS and BRAF are commoner in current and former smokers, so molecular typing and PD-L1 scoring now precede treatment in metastatic disease.

Nuclear medicine's role here is diagnostic and it is decisive. The staging work-up runs from history, examination and contrast-enhanced chest CT to 18F-FDG PET, with tissue taken by bronchoscopy, mediastinoscopy or anterior mediastinotomy. Across 44 studies and 2,865 patients, FDG PET detected mediastinal nodal metastasis with a pooled sensitivity of 74% (95% CI 69-79) and specificity of 85% (95% CI 82-88), against roughly 61% and 79% for CT, and a randomised trial found that adding FDG PET to conventional staging significantly reduced the number of thoracotomies. It does not replace sampling: because false positives are frequent enough that forgoing mediastinoscopy on a PET-positive node was judged unsafe, a positive mediastinum is still biopsied, while PET's main practical value is finding the distant deposit that makes surgery futile. Since 1 January 2025 the reporting task has changed shape: the ninth edition of TNM splits N2 into N2a (single-station) and N2b (multiple-station) and M1c into M1c1 (several metastases in one organ system) and M1c2 (several organ systems), so a scan report now has to count nodal stations and organ systems rather than simply call the mediastinum positive.

What is moving. China approved technetium (99mTc) pexiretide in April 2026, an integrin alpha-v-beta-3 RGD peptide that puts the same staging question on a SPECT/CT scanner, which matters where SPECT capacity far exceeds PET capacity. 68Ga-FAPI-04, which targets the fibroblast scaffolding rather than glucose metabolism, detected primary NSCLC with 96.7% sensitivity and staged nodal stations at 72.0% sensitivity and 93.1% specificity in a 91-patient series, the specificity FDG lacks. Research tracers including 18F-FLT for proliferation and 18F-F-AraG for T-cell activity are in trials aimed at response rather than extent. Therapy is the gap: no radiopharmaceutical is approved to treat lung cancer of any histology anywhere, and the alpha-emitting DLL3 programmes now in the clinic are aimed at small-cell disease, which has its own record.

Symptoms, diagnosis and staging

Sources: NCI PDQ: non-small cell lung cancer treatment (health professional), Implementation of the 9th TNM for lung cancer: practical points (2025)

How it shows

Worsening cough, chest pain, haemoptysis, malaise, weight loss, breathlessness and hoarseness are the commonest presenting complaints.
Many tumours are found incidentally on chest imaging performed for another reason.
Symptoms may come from local invasion or compression of adjacent structures, for example dysphagia from oesophageal compression or hoarseness from laryngeal nerve involvement.

How it is confirmed

Tissue is obtained by bronchoscopy, mediastinoscopy or anterior mediastinotomy; histology is classified under the WHO/IASLC system.
Imaging work-up is contrast-enhanced chest CT followed by 18F-FDG PET, with bone scintigraphy and brain CT or MRI when distant spread is suspected.
Molecular testing for EGFR, ALK, ROS1, BRAF, RET, NTRK, MET, KRAS and HER2, plus PD-L1 immunohistochemistry, directs systemic treatment in advanced disease.

How it is staged

The ninth edition of TNM has applied since 1 January 2025.
N2 is now split into N2a (single nodal station) and N2b (multiple stations); M1c is split into M1c1 (multiple metastases in a single organ system) and M1c2 (metastases in multiple organ systems). The T categories are unchanged from the eighth edition.
Pathological staging requires examination of the tumour, knowledge of the resection margins and determination of nodal status; clinical and pathological stage can differ.

State of the art

18F-FDG PET/CT is the staging backbone. Pooled across 44 studies and 2,865 patients, sensitivity for mediastinal nodal metastasis was 74% (95% CI 69-79) and specificity 85% (95% CI 82-88), against about 61% and 79% for CT; the median prevalence of mediastinal metastases in those series was 29%.
PET changes management mainly by finding disease outside the chest. A randomised study found significantly fewer thoracotomies when FDG PET was added to conventional staging, but the trials disagree on how many futile operations it prevents, and PET-positive mediastinal nodes still require sampling.
The ninth edition of TNM, effective 1 January 2025, leaves the T categories unchanged but divides N2 into N2a (single-station) and N2b (multiple-station) and M1c into M1c1 (multiple metastases in one organ system) and M1c2 (metastases in multiple organ systems), which moves some patients to a lower stage group and puts the burden of counting stations and organ systems onto the imaging report.
Technetium (99mTc) pexiretide, approved by China's NMPA on 2 April 2026, is the first approved alternative that answers the nodal-staging question on SPECT/CT rather than PET/CT, a distinction that matters in health systems whose SPECT installed base is several times their PET capacity.
68Ga-FAPI-04 PET/CT detected the primary tumour with 96.7% sensitivity and 100% positive predictive value, and staged nodal stations with 72.0% sensitivity, 93.1% specificity and 89.4% accuracy, in 91 patients with NSCLC; uptake correlated with fibroblast activation protein expression in resected specimens.
No radiopharmaceutical therapy is approved for lung cancer of any histology. Targets identified in lung tumours (fibroblast activation protein, integrin alpha-v-beta-3) are so far used for imaging only, and the alpha-emitting DLL3 programmes in the clinic are directed at small-cell disease.

Anatomy and lymph node drainage

Lungs, pleura and mediastinum: subsites and node stations · wireframe schematic, not to scale

Central tumours arise in the large airways, peripheral ones in the alveoli; both drain to hilar then mediastinal nodes, and the pleural lining is a separate cancer site.

Subsites

Central airways (squamous, small-cell)Squamous cell carcinoma (about 25%; usually near a central bronchus) · Adenosquamous carcinoma
Periphery (adenocarcinoma)Adenocarcinoma (about 40% of all lung cancers; usually peripheral)
Apex (Pancoast)
Pleura (mesothelioma)Sarcomatoid carcinoma
Thymus (anterior mediastinum)Adenocarcinoma (about 40% of all lung cancers; usually peripheral) · Squamous cell carcinoma (about 25%; usually near a central bronchus) · Large cell carcinoma (about 10%) · Adenosquamous carcinoma · Sarcomatoid carcinoma

Regional lymph nodes

hilar (N1)
mediastinal (N2)
supraclavicular (N3)

Same organ: Small-cell lung cancer, Lung neuroendocrine tumours (typical and atypical carcinoid)

Preclinical models

10 cell lines, 4 mouse models and 7 repositories are listed for this cancer.

Who gets it and what has changed

Non-small-cell histologies are the large majority of that total.

Show survival figures (2)

Averages across everyone diagnosed, often years ago. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.

Lung cancer ranks first worldwide in both incidence and mortality: GLOBOCAN 2024 estimates 2,637,005 new cases (age-standardised rate 23.9 per 100,000) and 1,861,839 deaths (16.3 per 100,000) a year.
The NCI estimated 226,650 new US cases and 124,730 deaths for 2025, small-cell and non-small-cell combined, making it the leading cause of cancer death in the United States.

Group

lung

What is being done about this

Finding cancer earlier

Available now

FDG PETStandard of care

In trials

FAPI PETPhase 3
Fluorothymidine F-18 (FLT)Phase 2

Ideas and roadmaps

Nothing recorded yet.

Also on Nuclide: Roadmaps.

Advanced diseaseShow where advanced disease can reach, and what treats itThe sites decide which scans are done at staging and follow-up, and every site listed has a treatment approach.

Most people reading this do not have advanced disease. The map describes what can happen over the whole course of the illness, across autopsy and registry series; today's staging scans find spread earlier, and each site has treatments, from focused radiotherapy for a few spots to drugs that reach the brain.

What helpsA matched pill for each driver (osimertinib, lorlatinib, selpercatinib and others, most of which reach the brain), PD-(L)1 immunotherapy for the rest, ADCs after progression, and SBRT for a few sites.

What is being done about this

Advanced and metastatic disease

Available now

CT (computed tomography)Standard of care
PET/CTStandard of care
Technetium (99mTc) pexiretideApproved
Technetium Tc-99m medronate (MDP)Approved

In trials

Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLCActive

Ideas and roadmaps

Nothing recorded yet.

Also on Nuclide: Indications.

Other lung and pleuramost common
Bonemost common
Braincommon
Adenocarcinoma and EGFR- or ALK-driven tumours spread to the brain often; brain MRI is part of staging.
Livercommon
Adrenal glandscommon
Distant lymph nodescommon

Standard of care

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Screening in people at risk

Annual low-dose CT for adults aged 50 to 80 with a 20 pack-year smoking history who still smoke or quit within the past 15 years; stopped after 15 smoke-free years or when a competing health problem limits benefit.

USPSTF final recommendation statement, 9 March 2021

CT (computed tomography)

Diagnosis and initial staging

History, examination, laboratory tests, chest radiograph and contrast-enhanced chest CT, then 18F-FDG PET; tissue obtained by bronchoscopy, mediastinoscopy or anterior mediastinotomy.

NCCN Guidelines: Non-Small Cell Lung Cancer

CT (computed tomography)FDG PET PET/CTFludeoxyglucose F-18 (FDG)

Mediastinal nodes positive on PET

Pathological confirmation before a curative-intent plan is abandoned, because the false-positive rate makes PET alone an unsafe basis for withholding surgery.

NCCN Guidelines: Non-Small Cell Lung Cancer

FDG PET PET/CT

Suspected distant spread

Bone scintigraphy and CT or MRI of the brain when symptoms, signs, laboratory findings or perceived risk suggest metastatic disease that PET may not resolve.

NCI PDQ, NSCLC treatment (health professional)

Technetium Tc-99m medronate (MDP)CT (computed tomography)

Resectable early-stage disease

Surgery with mediastinal nodal evaluation, with adjuvant systemic therapy for larger or node-positive tumours; stereotactic body radiotherapy or conventional radiotherapy where the patient is inoperable.

NCCN Guidelines: Non-Small Cell Lung Cancer

Locally advanced unresectable disease

Radiotherapy combined with chemotherapy, with long-term survival achievable in a minority.

NCI PDQ, NSCLC treatment (health professional)

Advanced metastatic disease

Systemic therapy directed by molecular typing and PD-L1 score: targeted agents where a driver alteration is present, chemotherapy and immunotherapy otherwise, alongside supportive care.

NCCN Guidelines: Non-Small Cell Lung Cancer

Subtypes & biomarkers

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Subtypes

Adenocarcinoma (about 40% of all lung cancers; usually peripheral)
Squamous cell carcinoma (about 25%; usually near a central bronchus)
Large cell carcinoma (about 10%)
Adenosquamous carcinoma
Sarcomatoid carcinoma
Salivary gland-type tumours of the lung

Biomarkers clinicians test

EGFR
ALK
ROS1
BRAF
RET
NTRK1, NTRK2, NTRK3
MET
KRAS
HER2
PD-L1 tumour proportion score (22C3 immunohistochemistry)
Stage (ninth-edition TNM) remains the dominant treatment determinant

How often this target appears

Target / alteration	Prevalence	Measure	Source
HER3 (ERBB3)	83%	immunohistochemistry, any expression, published series	PMC

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail.

History

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2010Revised international staging system adopted by AJCC and UICC
Built from a clinical database of more than 5,000 patients; gave greater prognostic specificity to the stage groups.
2021USPSTF widens low-dose CT screening
Final statement of 9 March 2021: annual LDCT for adults aged 50 to 80 with a 20 pack-year history who smoke or quit within 15 years, lowering both the age and pack-year thresholds.
2025Ninth-edition TNM takes effect on 1 January
N2 splits into N2a and N2b, M1c into M1c1 and M1c2; T categories unchanged.
PET/CT
2026China approves technetium (99mTc) pexiretide for nodal staging
NMPA approval on 2 April 2026 of an integrin alpha-v-beta-3 RGD peptide for SPECT/CT assessment of regional lymph nodes in suspected lung cancer.
Technetium (99mTc) pexiretide

What changed

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Dated changes read from the records linked to this indication: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.

All 11 changes by month →

FollowWatch this record and Saved shows what changed since you last looked.Follow by feed

In development

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What is in development for Non-small cell lung cancer, drawn from the whole corpus: 8 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.

Drugs in phase 2 · 2

Phase 2PET tracer

Gallium-68 FAPI-46

Phase 2PET tracer

Fluorothymidine F-18 (FLT)

Drugs in phase 1 · 1

Phase 1Alpha-emitting radioligand (FAP-alpha targeted)

Lead-212 PSV359

Technologies being tested · 2

FAPI PET Radiomics

Trials under way · 3

Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG · phase 2 · CellSight Technologies, Inc.
Efficacy and Safety of a Single Dose of LS301-IT for Fluorescence Intraoperative Molecular Imaging (IMI) for Patients Undergoing Lung Cancer Resection for Non Small Cell Lung Cancer · phase 2 · Integro Theranostics
Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLC · phase 3 · Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Open problems and what is being done

FDG PET misses about a quarter of mediastinal nodal metastases, so a negative mediastinum on PET does not reliably spare a patient invasive staging when the pre-test probability is high.
What is being done about this
Advanced and metastatic disease
Available now
CT (computed tomography)Standard of care
PET/CTStandard of care
Technetium (99mTc) pexiretideApproved
Technetium Tc-99m medronate (MDP)Approved
In trials
Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLCActive
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Indications.
False positives are frequent enough that a PET-positive mediastinal node cannot be treated as proof of spread; the money saved by skipping mediastinoscopy was judged not to justify the error rate.
What is being done about this
Advanced and metastatic disease
Available now
CT (computed tomography)Standard of care
PET/CTStandard of care
Technetium (99mTc) pexiretideApproved
Technetium Tc-99m medronate (MDP)Approved
In trials
Study Of Comparing SAF-189s With Crizotinib In First Line ALK-Positive Advanced and Metastatic NSCLCActive
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Indications.
Glucose metabolism is a non-specific target. FAP and integrin imaging offer higher specificity for nodal disease but neither has a regulatory approval outside China, and neither has been tested head-to-head against FDG in a registrational trial.
There is no theranostic pair in lung cancer: every approved agent here is diagnostic, and no radioligand therapy has reached approval in any lung histology.
The ninth-edition N2a/N2b and M1c1/M1c2 subdivisions require station-level and organ-system-level reporting that most existing structured-report templates and PET reporting software do not yet produce.
Most of the world's 2.6 million annual cases arise where PET capacity is thinnest, which is the practical argument for the SPECT-based alternative China approved rather than for a better PET tracer.
What is being done about this
Cost and access
Available now
Technetium Tc-99m albumin aggregated (MAA)Approved
In trials
Nothing recorded yet.
Ideas and roadmaps
Nothing recorded yet.
Also on Nuclide: Approvals and coverage by region.

Trials

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Trials recruiting now

Recruiting trials near you · live from ClinicalTrials.gov

Non-small cell lung cancer

condition: Non-small cell lung cancer

Open on ClinicalTrials.gov →

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