Integrate pathology, TNM stage, invasive nodal assessment, molecular drivers, PD-L1, cardiopulmonary reserve and patient priorities to select curative local, multimodality or advanced systemic treatment.
Non-small-cell lung cancer describes a group of epithelial lung malignancies dominated by adenocarcinoma and squamous carcinoma. Tobacco exposure remains the principal cause, but never-smokers can develop oncogene-driven adenocarcinoma and should not be clinically stereotyped. A peripheral early lesion may be incidental, while central disease produces cough, haemoptysis, collapse or recurrent infection. Apical tumours can invade brachial plexus and sympathetic chain; advanced disease commonly spreads to brain, bone, liver, adrenal and pleura.
The first therapeutic classification combines histology and TNM anatomy. Contrast CT maps primary, regional nodes and common metastatic sites. PET-CT improves whole-body staging when radical treatment is contemplated, but inflammatory uptake creates false-positive nodes and small or low-avidity disease creates false negatives. EBUS or EUS samples accessible mediastinal nodes, with surgical staging when a negative result remains discordant with high risk. Any solitary distant lesion that changes intent from curative to palliative deserves confirmation when safely feasible.
Cumulative smoking is the largest preventable cause, producing widespread bronchial DNA damage, but never-smokers also develop biologically distinct NSCLC.
Radon, asbestos, silica, diesel exhaust, air pollution and some workplace metals add risk with long latency and possible smoking interaction.
Prior radiotherapy, pulmonary fibrosis and chronic inflammatory lung disease increase risk through persistent tissue injury and genomic stress.
EGFR, ALK, ROS1, BRAF, MET, RET, KRAS and other alterations can create targetable growth dependence independent of clinical stereotype.
Accumulated driver activation and tumour-suppressor loss allow bronchial or alveolar epithelial cells to proliferate, resist death and evade repair.
Tumour invades airway, pleura, chest wall, vessels and nerves, causing cough, collapse, pain, bleeding, effusion and superior sulcus syndromes.
Spread through hilar and mediastinal nodes changes resectability and radiotherapy volume, making pathological nodal confirmation central to curative planning.
Circulating clones seed brain, bone, liver, adrenal and contralateral lung, while immune escape and molecular heterogeneity drive treatment resistance.
Cough, haemoptysis, unilateral wheeze, lobar collapse or recurrent infection suggests an endobronchial squamous or other central lesion.
A spiculated peripheral nodule or mass may be asymptomatic until pleural pain, distant spread or incidental imaging detection.
Shoulder and medial-arm pain, hand weakness, Horner syndrome or rib destruction indicates apical chest-wall and neural invasion.
Hoarseness, phrenic palsy, dysphagia or upper-body venous congestion suggests local nodal or direct invasion affecting curative stage.
Seizure, bone pain, fracture, jaundice, hypercalcaemia, adrenal lesion or weight loss may reveal distant disease.
Driver alterations occur across ages and smoking histories and are identified by testing rather than phenotype.
Pneumonia, tuberculosis, fungal disease, sarcoidosis and organising inflammation can be FDG-avid and mimic primary or nodal cancer.
Neuroendocrine morphology, rapid dissemination and distinct immunohistochemistry define SCLC, whose staging and systemic treatment pathway differs.
A lung lesion in someone with another cancer may be metastatic disease or a second primary; morphology and molecular comparison can preserve curative options.
Granuloma, hamartoma and scar can remain stable or show characteristic imaging, but growth and high-risk morphology require governed nodule investigation.
Central tumour narrows bronchus, causing lobar collapse, retained secretion, recurrent post-obstructive pneumonia and eventual respiratory failure.
Pleural dissemination causes recurrent effusion, trapped lung, chest pain and a metastatic stage requiring symptom and systemic treatment planning.
Brain lesions cause seizure or pressure, while bone disease causes pain, fracture, hypercalcaemia and metastatic spinal cord compression.
Surgery, platinum therapy, targeted agents, checkpoint inhibitors and thoracic radiation can injure lung, marrow, kidney, nerves, heart and endocrine organs.
Sampling the highest relevant node or an accessible distant lesion may establish both histology and stage while conserving procedures.
Inflammation can be avid and microscopic nodal cancer can be missed, so tissue remains decisive when stage changes curative treatment.
A tumour may be anatomically resectable while the person cannot tolerate surgery, or physiologically fit while anatomy requires another radical modality.
Never-smoking and young age enrich some drivers but do not replace the national test result in any eligible patient.
Selected oligoprogression may be ablated while an otherwise effective targeted therapy continues, avoiding a premature whole-system switch.
Using a small cytology sample without conserving tissue for genomic and PD-L1 testing.
Treating PET-positive mediastinal nodes as proven without tissue when the result changes curative management.
Abandoning curative intent because of one unconfirmed distant lesion.
Calling a tumour inoperable without separating anatomical resectability from cardiopulmonary fitness.
Starting non-urgent advanced therapy before the genomic result that determines the preferred first sequence.
Assuming new lung change on immunotherapy is progression without assessing pneumonitis, infection and embolism.
Using an outdated remembered NICE drug indication instead of checking the current biomarker and stage criteria.
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A potentially resectable peripheral NSCLC has an FDG-avid mediastinal node on PET-CT but no distant disease. What is the best next staging step before abandoning a surgical pathway?
National guidance is shown before implementation-dependent detail. Typical adult dose examples remain subject to patient factors, contraindications and the live BNF or specialist protocol. Source check completed 27 Aug 2026; clinical approval remains outstanding.
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Advanced NSCLC is a set of molecular diseases. Adequate genomic profiling and PD-L1 testing should return before a non-urgent first regimen because EGFR, ALK and other actionable alterations can make targeted treatment preferable and influence later immunotherapy safety. Without an actionable driver, PD-L1, histology, performance and organ function guide immunotherapy alone or combined with chemotherapy. At apparent progression, distinguish diffuse cancer growth from oligoprogression and immune or radiation change before abandoning an otherwise effective systemic strategy.
Confirm the qualifying alteration and indication. Monitor ECG and QT, electrolytes, ventricular function when indicated, eye symptoms and blood count and investigate new breathlessness urgently for interstitial lung disease.
Immune toxicity can affect any organ and occur after stopping; review autoimmune disease, transplant, infection and immunosuppression and hold treatment for clinically significant suspected toxicity.
Check DPD status when fluoropyrimidines are involved and regimen-specific marrow, renal, hearing, neurological, emesis and thrombosis risks; cisplatin and carboplatin are not interchangeable without reason.