Pathophysiology
Cigarette smoke induces TP53, KRAS and EGFR mutations. Adenocarcinoma arises peripherally from type II pneumocytes (most common in never-smokers, EGFR/ALK driven). Squamous and small cell carcinomas are central and strongly smoking-related; small cell derives from neuroendocrine cells.
Sources: NCCN Non-Small Cell Lung Cancer (v3.2025); NCCN Small Cell Lung Cancer (v2.2025); USPSTF Lung Cancer Screening (JAMA 2021;325:962)
Clinical presentation
Cough, haemoptysis, chest pain, weight loss, recurrent pneumonia. Superior vena cava syndrome (facial oedema, distended neck veins), Pancoast tumour (shoulder pain, Horner syndrome, C8-T1 weakness), and paraneoplastic syndromes: SIADH and Cushing (small cell), hypercalcaemia (squamous, PTHrP), Lambert-Eaton myasthenic syndrome (small cell).
Screening & diagnosis
USPSTF: annual low-dose CT for adults 50-80 y with >=20 pack-years, current or quit within 15 y. Diagnosis: contrast CT, PET-CT for staging, biopsy (bronchoscopy for central, CT-guided for peripheral), brain MRI for stage >=II. NSCLC molecular panel (EGFR, ALK, ROS1, KRAS G12C, BRAF, MET, RET, NTRK, PD-L1).
Management - NSCLC
Stage I-II: lobectomy + mediastinal LN dissection; adjuvant osimertinib for EGFR-mutant, atezolizumab for PD-L1 >=1%. Stage III: chemoradiation + consolidation durvalumab. Stage IV: targeted therapy for driver mutations (osimertinib for EGFR; alectinib for ALK); PD-L1-directed immunotherapy +/- chemotherapy otherwise.
Management - SCLC
Limited stage: cisplatin/etoposide + concurrent thoracic radiation + prophylactic cranial irradiation. Extensive stage: platinum/etoposide + atezolizumab or durvalumab. Highly chemosensitive but relapses rapidly.
