Key Facts

Lung cancer remains the leading cause of cancer death worldwide and in the UK. Advances in molecular profiling, targeted therapy, and immunotherapy have significantly improved outcomes for selected patients.

Epidemiology

• UK incidence: approximately 48,500 new cases per year (3rd most common cancer)
• Mortality: approximately 35,000 deaths per year (leading cause of cancer death)
• Peak incidence: 70-74 years
• Male:female ratio approaching 1:1 (increasing in women)
• 5-year survival: approximately 15-16% overall; 55-60% for Stage I
• NHS Targeted Lung Health Check programme being rolled out for early detection

Aetiology

• Smoking (85-90%): dose-response relationship; risk proportional to pack-years; risk declines after cessation but never returns to baseline
• Passive smoking: 20-30% increased risk
• Occupational exposure: asbestos (synergistic with smoking), radon, arsenic, chromium, nickel
• Air pollution: estimated to contribute to 1-2% of lung cancers
• Genetic: family history increases risk 1.5-2×; EGFR mutations more common in non-smokers/East Asian populations
• Pre-existing lung disease: COPD, pulmonary fibrosis

Pathophysiology

• Adenocarcinoma (40%): peripheral location; most common subtype; common in non-smokers; glandular differentiation; EGFR, ALK, KRAS mutations
• Squamous cell carcinoma (25-30%): central location, cavitating; strongly associated with smoking; may produce PTHrP (hypercalcaemia)
• Large cell carcinoma (10%): poorly differentiated; often peripheral
• Small cell lung cancer (15%): central, rapidly growing, early metastasis; neuroendocrine origin; strongly associated with smoking; paraneoplastic syndromes common (SIADH, Lambert-Eaton, Cushing)

Local Symptoms

• Persistent cough (most common presenting symptom)
• Haemoptysis
• Dyspnoea
• Chest pain (pleuritic or dull ache)
• Recurrent pneumonia (post-obstructive)

Local Invasion

• Hoarseness (recurrent laryngeal nerve palsy)
• Dysphagia (oesophageal compression)
• SVCO (facial swelling, distended veins)
• Pancoast tumour: shoulder/arm pain, Horner syndrome (miosis, ptosis, anhidrosis), T1 weakness
• Phrenic nerve palsy (raised hemidiaphragm)

Paraneoplastic Syndromes

• SIADH (hyponatraemia) - SCLC
• Ectopic ACTH (Cushing) - SCLC
• Lambert-Eaton myasthenic syndrome - SCLC
• Hypercalcaemia (PTHrP) - squamous cell
• Hypertrophic pulmonary osteoarthropathy (HPOA) - clubbing, periostitis

Red Flags

• Haemoptysis at any age
• Persistent cough >3 weeks with risk factors
• Unexplained weight loss with chest symptoms
• New hoarseness with smoking history
• Recurrent pneumonia in same location

Bedside

• CXR: first-line investigation (lesion visible in ~75%); hilar mass, peripheral nodule, pleural effusion, collapse, mediastinal widening
• Sputum cytology: low sensitivity (~30%) but specific if positive
• Pulse oximetry

Bloods

• FBC, U&Es (Na⁺ for SIADH), LFTs, calcium, LDH, albumin
• Tumour markers: not routinely used for diagnosis

Imaging

• CT chest/abdomen/adrenals with contrast: staging; characterise primary lesion and assess lymph nodes, liver, adrenals
• PET-CT: staging and assessment of mediastinal lymph nodes; guides biopsy site
• MRI brain: if SCLC or NSCLC Stage IB+ (brain metastasis screening)
• Bone scan: if bone pain or raised ALP

Special Tests

• Tissue biopsy for histological diagnosis:
  • CT-guided percutaneous biopsy (peripheral lesions)
  • Bronchoscopy ± EBUS (endobronchial USS-guided biopsy) for central lesions and mediastinal lymph nodes
  • Thoracoscopy (VATS) for pleural disease
• Molecular profiling (NSCLC, non-squamous): EGFR mutations, ALK rearrangement, ROS1 rearrangement, BRAF V600E, KRAS G12C, PD-L1 expression (TPS), NTRK fusions
• Pulmonary function tests: pre-operative assessment (FEV1, TLCO); predict postoperative lung function

Non-pharmacological

• MDT discussion (thoracic surgery, medical oncology, clinical oncology, radiology, pathology, respiratory medicine, CNS)
• Smoking cessation
• Pulmonary rehabilitation (pre-operative)
• Psychological support

Pharmacological

• Early-stage NSCLC (Stage I-II):
  • Surgery (lobectomy) + adjuvant chemotherapy if Stage IB-IIIA (cisplatin-based, e.g. cisplatin + vinorelbine × 4 cycles)
  • Adjuvant osimertinib for resected EGFR-mutant NSCLC (ADAURA trial)
  • Adjuvant atezolizumab for resected PD-L1+ NSCLC (IMpower010)
• Locally advanced NSCLC (Stage III):
  • Concurrent chemoradiotherapy (cisplatin + etoposide or cisplatin + vinorelbine + 60-66 Gy RT) → durvalumab maintenance (PACIFIC trial)
• Advanced NSCLC (Stage IV):
  • PD-L1 ≥50%, no actionable mutation: pembrolizumab monotherapy (KEYNOTE-024)
  • PD-L1 <50%, no mutation: pembrolizumab + carboplatin + pemetrexed (KEYNOTE-189)
  • EGFR mutation: osimertinib (FLAURA trial)
  • ALK rearrangement: alectinib (ALEX trial)
  • BRAF V600E: dabrafenib + trametinib
  • KRAS G12C: sotorasib (CodeBreaK 100)
• SCLC:
  • Limited stage: cisplatin 80mg/m² + etoposide 100mg/m² × 4 cycles + concurrent thoracic RT (45 Gy); prophylactic cranial irradiation (PCI) if response
  • Extensive stage: carboplatin + etoposide + durvalumab × 4 cycles → durvalumab maintenance (CASPIAN trial); PCI if response

Surgical/Interventional

• Lobectomy (preferred) or pneumonectomy: curative for early-stage NSCLC
• VATS (video-assisted thoracoscopic surgery): minimally invasive; preferred approach
• SABR/SBRT: for medically inoperable early-stage NSCLC (e.g. 54 Gy in 3 fractions)
• Endobronchial interventions: stenting, debulking, laser for airway obstruction
• Pleural procedures: talc pleurodesis for malignant effusion, IPC insertion

Referral Criteria

• Suspected lung cancer: urgent 2-week wait referral per NICE NG12
• All confirmed: MDT discussion before any treatment
• Molecular testing results: to determine targeted therapy eligibility
• Palliative care: early involvement recommended (improves quality of life and survival)

• Overall 5-year survival: 15-16% (all stages combined)
• Stage IA: 80-90% 5-year survival
• Stage IB: 68%
• Stage II: 50-60%
• Stage IIIA: 25-35%
• Stage IIIB-C: 10-15%
• Stage IV: 5-10% (improving with immunotherapy and targeted therapy)
• SCLC limited stage: median survival 15-20 months; 5-year survival 10-15%
• SCLC extensive stage: median survival 10-12 months; rare long-term survivors

Lung Cancer TNM Staging (8th Edition Summary)

Key Landmark Trials