Lung Cancer — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Lung cancer is the leading cause of cancer-related death worldwide, accounting for approximately 1.8 million deaths per year — more than breast, colorectal, and prostate cancer combined. It is classified into two major types based on cell appearance and behaviour: non-small cell lung cancer (NSCLC — 85% of cases), which includes adenocarcinoma (most common subtype in non-smokers and women; arises in peripheral lung), squamous cell carcinoma (strongly associated with smoking; arises centrally near bronchi), and large cell carcinoma; and small cell lung cancer (SCLC — 15%), which is almost exclusively caused by smoking, grows rapidly, and commonly presents with metastatic disease. The poor overall prognosis (5-year survival approximately 15-20%) is largely due to the majority (70-75%) presenting at an advanced, unresectable stage. Molecular profiling has transformed NSCLC treatment — activating driver mutations (EGFR, ALK, ROS1, BRAF V600E, MET, RET, KRAS G12C) and PD-L1 expression now guide personalised treatment. Low-dose CT (LDCT) lung cancer screening in high-risk smokers detects earlier-stage cancers and reduces lung cancer mortality by 20%.

Cigarette smoking is the single most important cause of lung cancer — responsible for approximately 85% of all cases. The relative risk of lung cancer is 15-25x higher in smokers compared with never-smokers; risk is proportional to pack-years smoked (packs per day × years of smoking). Risk reduces progressively after stopping but does not return to never-smoker levels for 15-20 years. Other tobacco products (cigars, pipes, smokeless tobacco) also increase risk. Radon gas: a naturally occurring radioactive gas produced by uranium decay in soil and rock — the leading cause of lung cancer in non-smokers; accumulates in homes (particularly ground floors in granite-rich regions). The UK has particularly high radon levels in areas of Devon, Cornwall, Somerset, and Derbyshire. Asbestos: asbestos fibres cause mesothelioma and significantly increase lung cancer risk (synergistic with smoking — 50-90x risk in asbestos-exposed smokers versus non-smokers who do not work with asbestos). Occupational exposures: arsenic, chromium, nickel, beryllium, silica, polycyclic aromatic hydrocarbons. Air pollution: outdoor PM2.5 particulate pollution, indoor air pollution (cooking with solid fuels, biomass). Genetics: first-degree family history of lung cancer increases risk 2-fold independently of smoking; germline mutations in EGFR (rare) and other genes. Never-smoker lung cancer (approximately 15%): predominantly adenocarcinoma; driver mutations (EGFR, ALK, ROS1) more common; women more commonly affected; secondhand smoke, radon, air pollution, and occupational exposures contribute.

Lung cancer is frequently asymptomatic in early stages — symptoms typically develop when the tumour is locally advanced or has spread. Respiratory symptoms: persistent new or worsening cough lasting more than 3 weeks, haemoptysis (coughing up blood — even a single episode warrants urgent investigation), dyspnoea (breathlessness — from tumour obstruction, pleural effusion, or SVCO), wheeze or stridor (large airway obstruction), and recurrent chest infections or pneumonia. Chest symptoms: pleuritic chest pain (pleural invasion), dull aching chest pain, and hoarseness (recurrent laryngeal nerve involvement — particularly left hilum tumours compressing the left RLN causing vocal cord palsy). Systemic symptoms: unexplained weight loss (loss of 5% or more body weight), fatigue, and anorexia. Symptoms from local invasion: dysphagia (oesophageal involvement), Horner's syndrome (ptosis, miosis, anhidrosis — superior sulcus/Pancoast tumour invading the cervical sympathetic chain), brachial plexopathy — arm and shoulder pain from Pancoast tumour; superior vena cava obstruction (SVCO — facial and neck swelling, dilated neck veins, arm oedema, headache — emergency). Metastatic symptoms: bone pain and fractures (bone metastases — lung cancer most commonly metastasises to bone, brain, liver, and adrenal glands), neurological symptoms (brain metastases — headache, seizures, focal weakness), and right upper quadrant pain (liver metastases). Paraneoplastic syndromes (particularly SCLC): syndrome of inappropriate ADH (SIADH — hyponatraemia), ectopic ACTH production (Cushing's), Lambert-Eaton myasthenic syndrome (LEMS — proximal weakness), and hypercalcaemia (squamous cell carcinoma — PTHrP production).

Chest X-ray: first investigation for suspected lung cancer — may show a pulmonary mass, hilar enlargement, pleural effusion, or collapse; however, 25% of lung cancers are not visible on CXR. CT thorax with contrast (CT chest, abdomen, and pelvis for staging): essential — characterises the primary tumour (size, location, contact with structures), identifies mediastinal lymph node involvement, and detects distant metastases. PET-CT (positron emission tomography-CT): the gold standard for staging — differentiates malignant from benign lymph nodes and detects unsuspected distant metastases; prevents futile surgery and identifies oligometastatic disease potentially suitable for curative-intent treatment. Tissue diagnosis — biopsy: essential before treatment. Methods: CT-guided percutaneous lung biopsy (peripheral lesions), bronchoscopy with EBUS (endobronchial ultrasound — mediastinal lymph node sampling), navigational bronchoscopy, or surgical biopsy via VATS (video-assisted thoracoscopic surgery). Molecular profiling (all NSCLC): EGFR mutations (exons 18-21 — most commonly exon 19 deletion and L858R in exon 21), ALK rearrangements, ROS1 rearrangements, KRAS G12C, BRAF V600E, MET exon 14 skipping, RET rearrangements, HER2 amplification. PD-L1 expression (tumour proportion score — TPS) by immunohistochemistry: determines immunotherapy eligibility. Liquid biopsy (ctDNA from blood): an alternative when tissue biopsy is not feasible or to monitor treatment response and detect resistance mutations. Brain MRI: for all NSCLC Stage III-IV and all SCLC — detects brain metastases. Staging: TNM staging (I-IV) — Stage I-II resectable, Stage III locally advanced, Stage IV metastatic.

Treatment is determined by histological type (NSCLC vs SCLC), stage, molecular profile, PD-L1 expression, and performance status. NSCLC — early stage (I-II): surgical resection (lobectomy via VATS or thoracotomy — preferred for anatomically suitable tumours); stereotactic ablative radiotherapy (SABR/SBRT — delivers precise high-dose radiotherapy, typically 3-5 fractions, for patients unfit for surgery) — achieves local control rates comparable to surgery in some studies. Adjuvant chemotherapy (cisplatin-based) for Stage IB-III after resection reduces recurrence risk. Adjuvant targeted therapy: osimertinib (EGFR inhibitor — 3 years) for Stage IB-IIIA EGFR-mutant NSCLC post-resection (ADAURA trial — dramatically improves disease-free and overall survival); adjuvant immunotherapy (atezolizumab or pembrolizumab) for selected patients. NSCLC — locally advanced (Stage III): concurrent chemoradiation (cisplatin + etoposide or paclitaxel with radical radiotherapy) followed by durvalumab (anti-PD-L1 immunotherapy consolidation — PACIFIC trial — improves overall survival by 7-12 months). Some Stage IIIA resectable with surgery after induction chemoimmunotherapy. NSCLC — advanced (Stage IV) with driver mutation: targeted oral therapies — osimertinib (3rd generation EGFR TKI — for EGFR mutations — FLAURA/FLAURA2 trials), alectinib or lorlatinib (ALK inhibitors), sotorasib or adagrasib (KRAS G12C), dabrafenib+trametinib (BRAF V600E), selpercatinib (RET), capmatinib (MET exon 14). These achieve objective response rates of 50-80% and progression-free survival of 12-36 months. NSCLC — Stage IV without driver mutation: PD-L1 TPS above 50% — pembrolizumab monotherapy (KEYNOTE-024 trial); PD-L1 1-49% — pembrolizumab plus platinum chemotherapy; PD-L1 under 1% — platinum doublet chemotherapy (cisplatin or carboplatin + pemetrexed or docetaxel). SCLC — limited stage: concurrent chemoradiation (cisplatin/etoposide) with prophylactic cranial irradiation; extensive stage — platinum/etoposide chemotherapy plus atezolizumab immunotherapy (IMpower133 trial).

Lung cancer generates a wide spectrum of serious local and systemic complications. Superior vena cava obstruction (SVCO): tumour compression of the SVC causes facial and arm oedema, dilated neck veins, headache, and stridor — a medical emergency requiring urgent radiotherapy or endovascular stenting. Malignant pleural effusion: accumulation of fluid between the pleural layers causes breathlessness in up to 15% of lung cancer patients — drained by thoracocentesis or managed with pleurodesis. Haemoptysis: tumour erosion into pulmonary vessels causes blood-streaked sputum or, rarely, catastrophic haemorrhage. Brain metastases: present in 20-40% of NSCLC and up to 70% of SCLC patients — cause headache, seizures, cognitive decline, and focal neurological deficits; treated with stereotactic radiosurgery or whole brain radiotherapy. Pathological fractures: bone metastases weaken cortical bone, causing fractures with minimal trauma — particularly vertebral bodies, femur, and humerus; treated with radiotherapy and orthopaedic fixation. Spinal cord compression from vertebral metastases is a neurological emergency requiring urgent dexamethasone and radiotherapy. Paraneoplastic syndromes: SIADH causing severe hyponatraemia; Lambert-Eaton syndrome causing proximal muscle weakness; ectopic Cushing's syndrome. Treatment-related complications including immunotherapy-induced pneumonitis affect 3-5% of patients.

Smoking cessation is the single most effective preventive measure. Stopping smoking at any age reduces risk — the sooner, the greater the benefit. At age 30, stopping smoking returns lung cancer risk to near-normal within 15 years. NHS Stop Smoking Services, nicotine replacement therapy (NRT — patches, gum, inhalers, nasal spray), varenicline (Champix — partial nicotinic receptor agonist — most effective single pharmacotherapy), and bupropion (Zyban) all significantly improve quit rates (NRT plus counselling doubles quit rates compared to willpower alone). Radon reduction: UK Health Security Agency recommends testing for radon in homes in high-risk areas; if levels exceed the action level (200 Bq/m3), install radon sumps (positive pressure underfloor ventilation) and improve floor/wall sealing. LDCT lung cancer screening: NICE recommends offering LDCT screening annually for 3 years to people aged 55-74 who are current or ex-smokers (quit within 25 years) — UK national lung cancer screening programme ('Targeted Lung Health Checks') is being rolled out. LDCT screening reduces lung cancer mortality by approximately 20% (NLST trial) to 26% (NELSON trial). Occupational safety: compliance with asbestos regulations, proper PPE, and exposure monitoring for carcinogens. Outdoor air quality: clean air policies reduce PM2.5 particulate levels and long-term lung cancer risk. Indoor air quality: use extractor fans or ventilate when cooking with oil; avoid burning solid fuels indoors where alternatives exist.

Seek same-day emergency care for: superior vena cava obstruction (SVCO — swollen face, neck, and arms, dilated chest veins, headache), haemoptysis with haemodynamic instability, and stridor. See a GP urgently (2-week wait referral in UK): any unexplained haemoptysis (coughing blood), a persistent new cough lasting more than 3 weeks (particularly in a smoker over 40), unexplained weight loss with respiratory symptoms, chest X-ray changes suggesting a lung lesion, or a suspected lung cancer found incidentally on imaging. Routine review with a GP for: persistent cough, breathlessness, or hoarseness in a smoker — do not dismiss these as 'smoker's cough' without investigation. If eligible, enrol in the National Lung Health Check (LDCT screening) — age 55-74, current or recent ex-smoker. Early detection is the most important determinant of survival in lung cancer.