Lung Cancer
Leading cause of cancer death in the UK, with ~48,000 new cases and ~35,000 deaths per year. Classified into non-small cell (85%) and small cell (15%). Smoking accounts for ~85% of cases.
Key Facts
Most common cause of cancer death in the UK; ~48,000 new cases per year; ~35,000 deaths per year NSCLC (~85%): squamous cell carcinoma, adenocarcinoma, large cell carcinoma; SCLC (~15%): aggressive, early metastasis Smoking causes ~85% of lung cancers; risk proportional to pack-years Two-week wait referral (NICE NG12): if CXR suggests lung cancer, or unexplained haemoptysis in ≥40 years Staging: NSCLC uses TNM staging; SCLC classified as limited or extensive disease Curative surgery for early-stage NSCLC (stage I-IIIA); adjuvant chemotherapy if stage IB-IIIA Immunotherapy: pembrolizumab (anti-PD-1) first-line for advanced NSCLC with PD-L1 ≥50% (NICE TA531; KEYNOTE-024 trial) 5-year survival: overall ~16%; stage IA ~80%; stage IV ~5%
Overview
Key Facts
Lung cancer is the most common cause of cancer-related death in the UK and worldwide. It is classified into non-small cell lung cancer (NSCLC, ~85%) and small cell lung cancer (SCLC, ~15%), with distinct management approaches and prognoses.
Epidemiology
- ~48,000 new cases per year in the UK
- ~35,000 deaths per year (leading cancer killer)
- Male:female ratio ~1.2:1 (gap narrowing)
- Peak incidence: age 70-80
- 5-year survival: overall ~16% (improving with targeted/immunotherapy)
- NHS lung cancer screening: targeted screening with LDCT for high-risk populations being rolled out
Aetiology
- Smoking: ~85% of lung cancers; risk increases with pack-years; cessation reduces but never eliminates risk
- Passive smoking: 20-30% increased risk
- Occupational: asbestos (synergistic with smoking), radon gas, chromium, arsenic, nickel, silica
- Genetics: family history increases risk 2-3 fold
- Pre-existing lung disease: COPD, pulmonary fibrosis (increased adenocarcinoma risk)
- Air pollution: contributes to ~1-2% of cases
Pathophysiology
NSCLC:
- Squamous cell carcinoma: central, arises from bronchial epithelium; associated with smoking, cavitation, hypercalcaemia (PTHrP)
- Adenocarcinoma: peripheral, commonest overall (especially in non-smokers and women); arises from glandular epithelium
- Large cell carcinoma: peripheral, undifferentiated; poor prognosis
SCLC:
- Neuroendocrine origin; central location
- Extremely aggressive: rapid doubling time, early widespread metastasis
- Highly chemosensitive initially but rapid relapse
- Strong association with paraneoplastic syndromes (SIADH, ectopic ACTH, Lambert-Eaton)
Clinical Presentation
Typical Presentation
- Persistent cough (>3 weeks) or change in chronic cough
- Haemoptysis
- Chest pain
- Breathlessness
- Recurrent pneumonia (same lobe)
- Weight loss, anorexia, fatigue
- Hoarseness (recurrent laryngeal nerve palsy)
Local Invasion
- SVC obstruction: facial/arm oedema, distended neck veins, headache, plethora
- Pancoast tumour (apex): shoulder pain radiating down arm, Horner syndrome (miosis, ptosis, anhidrosis, enophthalmos)
- Phrenic nerve palsy: elevated hemidiaphragm, breathlessness
- Recurrent laryngeal nerve palsy: hoarse voice (left > right)
- Oesophageal compression: dysphagia
Paraneoplastic Syndromes
- Hypercalcaemia: PTHrP (squamous cell)
- SIADH: ADH secretion → hyponatraemia (SCLC)
- Ectopic ACTH: Cushing syndrome (SCLC)
- Lambert-Eaton myasthenic syndrome: proximal weakness improving with use (SCLC)
- Hypertrophic pulmonary osteoarthropathy (HPOA): finger clubbing, painful wrists/ankles
- Dermatomyositis/polymyositis: proximal weakness, skin rash
Red Flags
- Haemoptysis in smoker/ex-smoker >40 years — urgent 2WW referral
- CXR suspicious for lung cancer — urgent 2WW referral
- Persistent unexplained cough >3 weeks in high-risk patient
- Non-resolving pneumonia
- New finger clubbing
- SVC obstruction (medical emergency)
Differential Diagnosis
| Diagnosis | Key Features | Investigation |
|---|---|---|
| Pneumonia | Acute onset, fever, productive cough, response to antibiotics | CXR, CRP, cultures |
| Tuberculosis | Chronic cough, upper lobe cavitation, weight loss, night sweats | Sputum AFB, IGRA |
| Metastatic disease | Multiple pulmonary nodules, known primary | CT, biopsy |
| Sarcoidosis | Bilateral hilar lymphadenopathy, non-caseating granulomas | CXR, ACE level, biopsy |
| Lung abscess | Cavitating lesion, air-fluid level, foul sputum | CT, sputum MC&S |
| Benign pulmonary nodule | Incidental finding, stable on serial imaging, <6mm | CT surveillance |
| Mesothelioma | Asbestos exposure, pleural thickening, effusion | CT, pleural biopsy |
| Lymphoma | Mediastinal lymphadenopathy, B symptoms | CT, biopsy |
Diagnosis / Investigation
Bedside
- CXR: first-line — mass lesion, hilar lymphadenopathy, collapse, effusion, non-resolving consolidation
- Pulse oximetry: baseline
Bloods
- FBC: anaemia of chronic disease
- U&Es: hyponatraemia (SIADH)
- Calcium: hypercalcaemia (squamous cell, bone metastases)
- LFTs: hepatic metastases
- Coagulation: pre-biopsy
Imaging
- CT chest/abdomen/pelvis with contrast: staging — tumour size, lymph nodes, metastases
- PET-CT: metabolic staging; assess mediastinal nodes and distant metastases
- CT/MRI brain: staging for advanced disease or SCLC
- Bone scan: if bone pain or elevated ALP
Special Tests
- Tissue diagnosis:
- CT-guided percutaneous biopsy (peripheral lesions)
- Bronchoscopy with biopsy/brushings/BAL (central lesions)
- EBUS (endobronchial ultrasound): mediastinal lymph node sampling
- Mediastinoscopy: if EBUS non-diagnostic
- Pleural biopsy (if effusion)
- Molecular testing (NSCLC): EGFR mutations, ALK rearrangements, ROS1, PD-L1 expression, KRAS G12C — guide targeted therapy
- Pulmonary function tests: assess fitness for surgery (FEV₁, TLCO)
- Cardiopulmonary exercise testing (CPET): VO₂max assessment if borderline fitness
Management
Non-pharmacological
- MDT discussion: all cases discussed at lung cancer MDT
- Smoking cessation
- Nutritional support
- Palliative care referral early in advanced disease
- Psychological support and lung cancer CNS involvement
Pharmacological
NSCLC:
- Stage I-II: surgical resection ± adjuvant chemotherapy (cisplatin-based doublet if stage IB-II)
- Stage IIIA: neoadjuvant/adjuvant chemo ± radiotherapy ± surgery (MDT decision)
- Stage IIIB-C (unresectable): concurrent chemoradiotherapy → durvalumab maintenance (PACIFIC trial; NICE TA578)
- Stage IV: systemic therapy based on molecular markers
- PD-L1 ≥50%: pembrolizumab monotherapy first-line (KEYNOTE-024; NICE TA531)
- PD-L1 <50% or irrespective: pembrolizumab + platinum-based chemo (KEYNOTE-189; NICE TA683)
- EGFR mutation positive: osimertinib 80mg OD (FLAURA trial; NICE TA654)
- ALK rearrangement: alectinib 600mg BD (ALEX trial; NICE TA670)
- KRAS G12C: sotorasib (NICE TA)
SCLC:
- Limited disease: concurrent chemoradiotherapy (cisplatin + etoposide × 4-6 cycles + thoracic radiotherapy)
- Extensive disease: chemotherapy (carboplatin + etoposide) + atezolizumab (anti-PD-L1; IMpower133 trial; NICE TA803)
- Prophylactic cranial irradiation (PCI): if good response to first-line treatment
Surgical/Interventional
- Lobectomy: standard for stage I-II NSCLC
- VATS (video-assisted thoracoscopic surgery): preferred minimally invasive approach
- Pneumonectomy: if lobectomy insufficient
- Segmentectomy/wedge resection: if poor lung function
- SABR (stereotactic ablative radiotherapy): for early-stage NSCLC in patients unfit for surgery
- Radical radiotherapy: for unresectable locally advanced disease
- Stenting: SVC stent for SVC obstruction; endobronchial stent for airway obstruction
- Palliative radiotherapy: bone/brain metastases, SVC obstruction, haemoptysis
Referral Criteria
- Urgent 2WW referral (NICE NG12): CXR suspicious for lung cancer; unexplained haemoptysis >40 years
- All cases to lung cancer MDT
- Early palliative care referral for advanced disease (improves quality of life and survival — Temel 2010 NEJM)
Prognosis
- Overall 5-year survival: ~16%
- Stage IA: ~80% 5-year survival
- Stage IB: ~60%
- Stage II: ~40-50%
- Stage IIIA: ~25%
- Stage IIIB-C: ~10%
- Stage IV: ~5%
- SCLC limited: median survival ~15-20 months; 5-year ~10%
- SCLC extensive: median survival ~8-12 months; 5-year <5%
- Immunotherapy has improved advanced NSCLC median survival from ~12 months to ~20-24 months
- EGFR+ NSCLC with osimertinib: median PFS ~18 months
- UK lung cancer screening programme aims to improve stage-shift and survival
Other Relevant Information
TNM Staging Summary (8th Edition)
| Stage | T | N | M |
|---|---|---|---|
| IA1 | T1a (≤1cm) | N0 | M0 |
| IA2 | T1b (1-2cm) | N0 | M0 |
| IA3 | T1c (2-3cm) | N0 | M0 |
| IB | T2a (3-4cm) | N0 | M0 |
| IIA | T2b (4-5cm) | N0 | M0 |
| IIB | T3 | N0 | M0 |
| IIIA | T1-2/N2 or T3-4/N1 | Various | M0 |
| IIIB | T1-2/N3 or T3-4/N2 | Various | M0 |
| IV | Any T | Any N | M1 |
Paraneoplastic Syndromes by Cell Type
| Syndrome | Cell Type | Mechanism |
|---|---|---|
| Hypercalcaemia | Squamous | PTHrP |
| SIADH | Small cell | ADH |
| Cushing syndrome | Small cell | Ectopic ACTH |
| Lambert-Eaton | Small cell | Anti-VGCC antibodies |
| HPOA/clubbing | Any (especially squamous) | Unknown |
| Gynaecomastia | Large cell | Beta-hCG |