Lung Cancer — Symptoms, Causes & Treatment | MyMedicPlus

Lung cancer is the leading cause of cancer-related death worldwide, with approximately 2.2 million new cases and 1.8 million deaths annually — more than breast, colon, and prostate cancers combined. Non-small cell lung cancer (NSCLC) accounts for 80-85% of cases and includes three major histological subtypes: adenocarcinoma (most common, arising from peripheral glandular tissue, often carries targetable mutations including EGFR, ALK, and ROS1), squamous cell carcinoma (central, arising from bronchial epithelium, associated with heavy smoking), and large cell carcinoma (undifferentiated, aggressive). Small cell lung cancer (SCLC) constitutes 15-20% and is characterised by rapid growth, early metastasis, strong association with smoking, and extreme sensitivity to initial chemotherapy and immunotherapy. Lung cancer is staged using the TNM classification (Stages I-IV for NSCLC; limited versus extensive for SCLC). Five-year overall survival remains approximately 20% across all stages, reflecting the high proportion diagnosed at advanced stage due to late symptom onset. Early detection through low-dose CT screening in eligible smokers is transforming outcomes.

Cigarette smoking is the dominant cause of lung cancer, responsible for approximately 85% of cases, with risk increasing proportionally with pack-year exposure (packs per day multiplied by years smoked). Former smokers retain elevated risk for decades after cessation, though quitting at any age reduces absolute risk significantly. Secondhand smoke exposure accounts for 3,000 lung cancer deaths annually in the United States alone. Radon gas — a naturally occurring radioactive gas produced by uranium decay in soil and rocks — is the second leading cause, responsible for 10-15% of cases. Occupational carcinogens include asbestos (synergistic with smoking — 50-90x increased risk in asbestos workers who smoke), silica, chromium VI compounds, arsenic, nickel, and polycyclic aromatic hydrocarbons. Outdoor air pollution is classified as a Group 1 carcinogen by IARC. Never-smoker lung cancer is increasing globally, particularly adenocarcinoma in women, and is disproportionately associated with targetable oncogenic driver mutations (EGFR mutations in 15% of Western populations, ALK rearrangements in 5%, ROS1 in 1-2%), making comprehensive molecular profiling essential for all advanced NSCLC.

Most early-stage lung cancers are completely asymptomatic and are detected only on imaging performed for other reasons — underscoring the importance of screening programmes. When symptoms occur, they typically reflect advanced local or metastatic disease. Pulmonary symptoms include persistent cough (worsening or new in a smoker), haemoptysis (blood in sputum — even a single episode warrants urgent investigation), progressive dyspnoea, and chest pain (dull, pleuritic, or referred). Bronchial obstruction causes recurrent post-obstructive pneumonia in the same lobe. Hoarseness from left recurrent laryngeal nerve compression by mediastinal or aortopulmonary window nodes is a sign of locally advanced disease. Superior vena cava (SVC) obstruction from tumour or node compression causes facial oedema, arm swelling, headache, and distended neck veins — a clinical emergency. Horner's syndrome (ptosis, miosis, anhidrosis on one side of the face) from cervical sympathetic chain involvement indicates an apical Pancoast tumour. Systemic symptoms include unexplained weight loss exceeding 5% body weight, fatigue, anorexia, and finger clubbing. Paraneoplastic syndromes — SIADH (hyponatraemia), hypercalcaemia of malignancy, Cushing's syndrome, and Lambert-Eaton myasthenic syndrome — may precede the primary tumour diagnosis.

Annual low-dose CT (LDCT) lung cancer screening is recommended for adults aged 50-80 who have a 20 pack-year or greater smoking history and currently smoke or quit within the past 15 years — the NLST trial demonstrated a 20% relative reduction in lung cancer mortality. A solitary pulmonary nodule or suspicious mass requires urgent investigation. Chest CT with intravenous contrast defines tumour size, mediastinal and hilar lymph node involvement, and distant metastases. Tissue diagnosis is essential before treatment: bronchoscopy with bronchoalveolar lavage and biopsy accesses central lesions; CT-guided percutaneous needle biopsy accesses peripheral lesions; endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples mediastinal and hilar lymph nodes with minimal morbidity. PET-CT is the gold standard for TNM staging, identifying distant metastases missed by CT. Comprehensive molecular profiling of all advanced NSCLC tissue is now mandated by ESMO and NCCN guidelines: EGFR mutations (exons 19/21 most common), ALK rearrangements (FISH or IHC), ROS1, KRAS G12C, BRAF, MET exon 14, RET — all have approved targeted therapies. PD-L1 expression (TPS score on 22C3 IHC assay) guides immunotherapy selection. Brain MRI is standard for all Stage III-IV NSCLC and all SCLC at staging.

Treatment is highly stage- and histology-dependent. Stage I-II NSCLC: anatomical surgical resection (lobectomy via VATS or open thoracotomy) is the gold standard for operable patients; stereotactic body radiotherapy (SBRT/SABR) achieves local control rates exceeding 90% for inoperable Stage I disease. Adjuvant osimertinib (for EGFR-mutant Stage IB-IIIA NSCLC after resection) reduces disease-free survival events by 80%. Stage III NSCLC: concurrent platinum-based chemoradiotherapy followed by 12 months of durvalumab (anti-PD-L1) consolidation — the PACIFIC trial demonstrated significant overall survival benefit. Stage IV NSCLC with driver mutation: osimertinib for EGFR exon 19/21 mutations (median PFS 18-22 months); alectinib or lorlatinib for ALK rearrangements; entrectinib or crizotinib for ROS1; sotorasib or adagrasib for KRAS G12C; tepotinib or capmatinib for MET exon 14 skip mutations. Stage IV NSCLC without driver mutation: pembrolizumab monotherapy for PD-L1 TPS ≥50% (KEYNOTE-024); carboplatin/pemetrexed/pembrolizumab for non-squamous (KEYNOTE-189); carboplatin/paclitaxel/bevacizumab/atezolizumab or carboplatin/nab-paclitaxel/pembrolizumab for squamous. SCLC limited stage: platinum-etoposide with thoracic radiotherapy plus prophylactic cranial irradiation. SCLC extensive stage: platinum-etoposide with atezolizumab (IMpower133) or durvalumab (CASPIAN) significantly improves overall survival.

Lung cancer causes both disease-related and treatment-related complications. Malignant pleural effusion occurs in 15% of NSCLC patients, causing progressive dyspnoea requiring thoracocentesis or indwelling pleural catheter (IPC). Superior vena cava (SVC) syndrome from tumour or nodal compression causes acute facial and upper limb oedema, headache, and dyspnoea — managed with dexamethasone, stenting, or urgent radiotherapy. Brain metastases occur in 40-50% of advanced NSCLC and nearly all SCLC if untreated — causing headache, seizures, focal deficits, and cognitive decline; treated with stereotactic radiosurgery, whole-brain radiotherapy, or targeted therapy (for EGFR/ALK-mutant disease). Bone metastases cause pathological fractures and hypercalcaemia of malignancy — managed with zoledronic acid, denosumab, and radiotherapy. Paraneoplastic syndromes include SIADH (hyponatraemia — common in SCLC), ectopic ACTH secretion (Cushing's), Lambert-Eaton myasthenic syndrome (proximal weakness), and hypercalcaemia from PTHrP secretion in squamous cell carcinoma. Haemoptysis can be catastrophic in advanced disease involving central airways and major pulmonary vessels, requiring urgent bronchoscopic or angiographic intervention.

Smoking cessation is the single most impactful preventable action — the risk of developing lung cancer decreases progressively over 10-15 years after quitting and approaches near-baseline after 25 years; cessation pharmacotherapy with varenicline (Champix) or combination NRT approximately doubles 12-month abstinence rates. Radon gas testing and mitigation is recommended in all homes, particularly in regions with high geological radon — ventilation systems and radon-resistant construction reduce indoor radon to below 4 pCi/L. Occupational carcinogen exposure should be minimised with appropriate personal protective equipment and workplace regulation. Annual low-dose CT (LDCT) screening in eligible current or former heavy smokers (aged 50-80 with 20+ pack-year history, quitting within the past 15 years) reduces lung cancer mortality by 20-25% (NLST trial) through detection at early resectable stages — all eligible individuals should discuss LDCT screening with their GP. Avoiding indoor air pollution (wood-burning stoves, solid fuel cooking in enclosed spaces) and reducing outdoor exposure during high pollution days reduces cumulative carcinogen exposure.

See your GP urgently (within 2 weeks — UK urgent 2-week wait referral criteria) for: persistent cough lasting more than 3 weeks, particularly in a current or former smoker; haemoptysis (coughing up blood) — even a single episode requires urgent investigation; unexplained weight loss of more than 5% body weight over 1-3 months; persistent chest pain not explained by musculoskeletal cause; new or worsening shortness of breath or hoarseness; and recurrent chest infections. Seek emergency care immediately for: massive haemoptysis (large volume blood); signs of superior vena cava obstruction (rapid onset severe facial, arm, or neck swelling with distended neck veins); sudden onset breathlessness suggesting pulmonary embolism (common in cancer); and new neurological symptoms (severe headache, visual changes, focal weakness) suggesting brain metastases. If you are an eligible current or ex-smoker aged 50-80 with a 20 pack-year history, discuss annual low-dose CT (LDCT) lung cancer screening with your GP — screening reduces lung cancer mortality by 20-25% by detecting cancers at early resectable stages.