Clinical meaning
Lung cancer is classified into non-small cell (NSCLC, 85%) and small cell (SCLC, 15%). NSCLC subtypes include adenocarcinoma (most common, 40%), squamous cell carcinoma (25-30%), and large cell carcinoma. Adenocarcinoma harbors actionable molecular drivers in ~60% of cases: EGFR mutations (exon 19 deletion, L858R — respond to osimertinib), ALK rearrangements (respond to alectinib), ROS1, BRAF V600E, KRAS G12C (sotorasib), and MET exon 14 skipping. PD-L1 expression (tumor proportion score) predicts response to immune checkpoint inhibitors (pembrolizumab, nivolumab). TNM staging (8th edition) guides treatment: T (tumor size and invasion), N (lymph node involvement — N0 none, N1 ipsilateral hilar, N2 ipsilateral mediastinal, N3 contralateral), M (metastases). Stage I-II: surgical resection; Stage III: multimodal (chemoradiation ± surgery ± immunotherapy); Stage IV: systemic therapy guided by molecular profiling and PD-L1.
Diagnosis & workup
Diagnostics & workup: - Low-dose CT screening: annual for adults 50-80 years with >= 20 pack-year history who currently smoke or quit within 15 years - Tissue diagnosis: CT-guided biopsy, bronchoscopy with biopsy, or surgical biopsy for pathologic confirmation - Molecular profiling of NSCLC: EGFR, ALK, ROS1, BRAF, KRAS G12C, MET, RET, NTRK, HER2, PD-L1 immunohistochemistry - PET-CT: staging for nodal and distant metastatic disease; SUV > 2.5 concerning for malignancy - Brain MRI with contrast: staging baseline (brain metastases present in 10-20% at diagnosis) - PFTs: assess surgical candidacy (FEV1 and DLCO > 40% predicted for lobectomy, > 60% for pneumonectomy) - Mediastinoscopy or EBUS (endobronchial ultrasound): confirm N2/N3 disease before treatment planning - SCLC staging: limited stage (one radiation field) vs extensive stage (beyond one field)