Lung Cancer

Lung cancer is a high-yield topic for finals, given its prevalence and significant mortality. Approximately 48,000 new cases are diagnosed annually in the UK. NSCLC accounts for 85% of cases, with Adenocarcinoma being the most common subtype (35-40%), followed by Squamous Cell Carcinoma (30-35%). SCLC (15%) is highly aggressive and often metastatic at presentation. Early detection is improving with 'Lung Health Checks' (LDCT screening) for high-risk individuals. The NICE 2-week wait (2WW) referral criteria are critical to know: any patient >40 with unexplained haemoptysis, OR persistent/unexplained symptoms (>3 weeks) like cough, fatigue, chest pain, or weight loss, especially in smokers/ex-smokers. Diagnosis involves initial CXR, followed by CT Thorax/Abdomen. Histological confirmation via bronchoscopy (central lesions) or CT-guided biopsy (peripheral lesions) is essential. PET-CT is used for staging (TNM). Management varies significantly by type and stage: early NSCLC is primarily surgical, while advanced NSCLC benefits from targeted therapies and immunotherapy. SCLC is typically managed with chemotherapy and radiotherapy, but has a poorer prognosis. Palliative care is a significant component of management.

Lung cancer originates from malignant transformation of bronchial epithelial cells. Key carcinogens include tobacco smoke (polycyclic aromatic hydrocarbons), asbestos (synergistic with smoking), and radon. Adenocarcinomas typically arise from peripheral mucus-secreting glands. Squamous cell carcinomas arise from the bronchial epithelium, often after squamous metaplasia, and are typically central. SCLC originates from neuroendocrine Kultschitzky cells. Molecular pathology is vital for NSCLC, with Adenocarcinomas routinely screened for EGFR, ALK, ROS1 mutations, and PD-L1 expression to guide targeted therapy. TP53 mutations are common across all types. Asbestos exposure is a major risk factor for both bronchogenic carcinoma and mesothelioma (a distinct pleural malignancy).

Presentations are crucial for finals: persistent cough (>3 weeks), haemoptysis, dyspnoea, unexplained weight loss, and recurrent pneumonia. Examination findings: Clubbing (especially NSCLC), supraclavicular lymphadenopathy, and dullness to percussion (pleural effusion). Local invasion signs are high-yield:
- Horner’s Syndrome (Ptosis, Miosis, Anhydrosis) due to Pancoast tumour (apical lesion compressing sympathetic chain).
- Superior Vena Cava (SVC) Obstruction (facial swelling, distended neck veins, fixed raised JVP) – an oncological emergency.
- Recurrent laryngeal nerve palsy (hoarse voice) due to compression.
- Phrenic nerve palsy (raised hemidiaphragm on CXR) due to compression.
Paraneoplastic syndromes are frequently tested:
- Squamous Cell: Hypercalcaemia (PTHrP).
- Small Cell: SIADH (hyponatraemia), Ectopic ACTH (Cushing's syndrome), Lambert-Eaton syndrome (proximal muscle weakness, improves with use).
- Adenocarcinoma: Hypertrophic pulmonary osteoarthropathy (HPOA – painful wrists/ankles and clubbing).

Investigations are about diagnosis and staging.
- Imaging: Chest X-ray (first-line for mass, hilar enlargement, pleural effusion, collapse). CT Thorax/Abdomen with contrast (essential for staging, assessing nodal involvement, and guiding biopsy). PET-CT (detects occult metastases, assesses metabolic activity of nodes and primary tumour for staging).
- Biopsy: Essential for histological diagnosis and molecular profiling. Bronchoscopy with EBUS (Endobronchial Ultrasound) for central lesions and mediastinal nodes. CT-guided percutaneous biopsy for peripheral lesions. Pleural fluid cytology if effusion is present.
- Bloods: FBC, LFTs (assess liver mets), Calcium (check for hypercalcaemia), U&Es (hyponatraemia in SIADH).

Management is complex and multidisciplinary.
- NSCLC Early (Stage I-II): Surgical resection (lobectomy is gold standard) if patient is fit (e.g., FEV1 >1.5L). Stereotactic Ablative Radiotherapy (SABR) is an option for patients unfit for surgery.
- NSCLC Advanced (Stage III-IV): Chemotherapy (platinum-based regimens). Targeted therapy if specific mutations are present (e.g., Erlotinib for EGFR mutations, Crizotinib for ALK rearrangements). Immunotherapy (e.g., Pembrolizumab) if PD-L1 expression is high.
- SCLC: Chemotherapy (Cisplatin + Etoposide) combined with radiotherapy. Prophylactic Cranial Irradiation (PCI) is often given due to high risk of brain metastases.
- Palliative care: Crucial throughout the disease course. Radiotherapy for bone pain or haemoptysis. SVC stenting for SVC obstruction. Endobronchial lasers for airway obstruction. Pleural drainage (e.g., indwelling pleural catheters) for recurrent effusions.