Lung cancer

Overview

•Third most common cancer in UK but leading cause of cancer death - most diagnosed at advanced stage

•Smoking accounts for ~72% of diagnoses

•Broad division: small-cell lung cancer (SCLC) vs non-small-cell lung cancer (NSCLC) - determines all management decisions

Presentation

•Primary tumour: cough (most common), haemoptysis, dyspnoea, chest pain, recurrent pneumonia (post-obstructive collapse)

•Local extension:

•Hoarse voice - recurrent laryngeal nerve palsy (nerve loops under aortic arch)

•Dysphagia - oesophageal compression

•Diaphragmatic elevation - phrenic nerve palsy

•Pancoast syndrome - apical tumour invading brachial plexus (C8-T2) + sympathetic chain: shoulder/arm pain, intrinsic hand muscle wasting, Horner's syndrome (ptosis, miosis, anhidrosis)

•Constitutional: weight loss, fatigue, anorexia, finger clubbing, supraclavicular lymphadenopathy

🚨
SVC obstruction - facial and upper limb oedema, distended neck/chest wall veins, dyspnoea. Pemberton's sign: raising arms above head causes facial congestion/cyanosis. Requires urgent oncological management.

Investigations

•NICE urgent CXR (within 2 weeks) - offer to patients aged ≥40 with:

•Unexplained haemoptysis - direct 2-week-wait referral (not just CXR)

•≥1 unexplained symptom (cough, dyspnoea, chest pain, fatigue, weight loss, appetite loss) who has ever smoked or had asbestos exposure

•≥2 unexplained symptoms in a never-smoker

•Finger clubbing or supraclavicular/cervical lymphadenopathy

🥇 First-line

•Chest X-ray - hilar enlargement, peripheral opacity, pleural effusion, lobar collapse, mediastinal widening

•Contrast-enhanced CT chest/abdomen/pelvis - staging; assesses tumour, nodes, liver/adrenal/bone metastases

🥈 Second-line

•PET-CT - radioactive glucose tracer; identifies occult metastases and nodes not visible on CT

•Bronchoscopy with EBUS - direct visualisation of central tumours; real-time ultrasound-guided biopsy of mediastinal nodes; staging and tissue diagnosis

🏆 Gold standard

•Histological biopsy - mandatory before treatment; determines SCLC vs NSCLC and molecular markers (EGFR, ALK) for targeted therapy

⚠️
A normal CXR does NOT exclude lung cancer. If clinical suspicion remains high, proceed to CT regardless.

Management

•All decisions made at MDT - treatment determined by histological type (SCLC vs NSCLC) and stage (resectable vs non-resectable)

•NSCLC, resectable: surgical resection is curative intent; ± adjuvant chemotherapy; targeted therapy (erlotinib, osimertinib for EGFR+; crizotinib for ALK+) where molecular markers present

•NSCLC, non-resectable: chemoradiotherapy or palliative chemotherapy

•SCLC: chemotherapy-based (rarely resectable); highly chemosensitive initially but almost invariably metastatic at diagnosis

Classification and Location

SCLC vs NSCLC subtypes
FeatureSCLCNSCLC - SquamousNSCLC - Adenocarcinoma
LocationCentral (hilar)Central (hilar)Peripheral
AssociationHeavy smokingSmokingNon-smokers; EGFR/ALK mutations
Key paraneoplasticSIADH, ectopic ACTH, Lambert-EatonHypercalcaemia (PTHrP)Clubbing
Resectable?Rarely - almost always metastatic at diagnosisIf localisedIf localised

Feature	SCLC	NSCLC - Squamous	NSCLC - Adenocarcinoma
Location	Central (hilar)	Central (hilar)	Peripheral
Association	Heavy smoking	Smoking	Non-smokers; EGFR/ALK mutations
Key paraneoplastic	SIADH, ectopic ACTH, Lambert-Eaton	Hypercalcaemia (PTHrP)	Clubbing
Resectable?	Rarely - almost always metastatic at diagnosis	If localised	If localised

Paraneoplastic Syndromes

•SIADH (ectopic ADH) - hyponatraemia, confusion; SCLC

•Ectopic Cushing's (ectopic ACTH) - hypokalaemia, hypertension, hyperglycaemia; rapid onset, no typical Cushingoid habitus; SCLC

•Lambert-Eaton myasthenic syndrome - autoantibodies vs presynaptic voltage-gated calcium channels; proximal weakness that improves with repeated use (opposite to myasthenia gravis); SCLC

•Hypercalcaemia (PTHrP) - 'bones, groans, moans, stones'; squamous cell carcinoma (NSCLC)

🎯
Paraneoplastic syndromes may be the first and only presenting feature of lung cancer. Hyponatraemia, ectopic Cushing's, or Lambert-Eaton in a smoker = think SCLC first.

Prognosis and Mesothelioma

•NSCLC stage I after surgical resection: five-year survival can exceed 70%

•SCLC: generally poor; majority have extensive disease at diagnosis; median survival without treatment measured in weeks to months

•Mesothelioma: malignancy of pleural mesothelial cells; strongly linked to asbestos exposure; latency up to 45 years; prognosis very poor; chemotherapy with pemetrexed + cisplatin can modestly improve survival