Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing approximately 85% of all lung cancer cases. Lung cancer remains the lead…
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Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing approximately 85% of all lung cancer cases. Lung cancer remains the leading cause of cancer death in the United States, with approximately 238,000 new cases and 127,000 deaths annually. NSCLC encompasses three main histologic subtypes: adenocarcinoma (40%), squamous cell carcinoma (25–30%), and large cell carcinoma (10%). The field has been transformed by molecular profiling — targetable driver mutations (EGFR, ALK, ROS1, BRAF, MET, NTRK, RET, KRAS G12C) and PD-L1 immunotherapy have dramatically improved outcomes in selected patients.
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Persistent cough or change in chronic cough
Hemoptysis (coughing up blood)
Dyspnea (shortness of breath) — from tumor obstruction or pleural effusion
Chest pain (pleuritic or dull persistent)
Unintentional weight loss and anorexia
Hoarseness (recurrent laryngeal nerve involvement)
Dysphagia (esophageal compression)
Superior vena cava (SVC) syndrome: facial swelling, arm edema, venous distension
Pancoast syndrome (apex tumors): shoulder/arm pain, Horner syndrome
Paraneoplastic syndromes: hypercalcemia, SIADH, digital clubbing, hypertrophic osteoarthropathy
CT chest with contrast — initial imaging; size, location, mediastinal nodes, pleural involvement
PET-CT — staging, metabolic activity, distant metastases
Brain MRI — mandatory for stage III-IV (brain metastases common)
Tissue biopsy: bronchoscopy, CT-guided percutaneous needle biopsy, endobronchial ultrasound (EBUS), or surgical
Histologic subtyping: adenocarcinoma vs. squamous vs. large cell (IHC: TTF-1, napsin-A, p40, CK5/6)
Comprehensive molecular profiling: EGFR, ALK, ROS1, BRAF V600E, MET exon 14, KRAS G12C, NTRK, RET — reflex testing for all advanced non-squamous NSCLC
PD-L1 expression (22C3 assay) — guides first-line immunotherapy selection
Liquid biopsy (ctDNA) — for molecular profiling when tissue insufficient, or monitoring resistance
TNMM staging: I–IVB
Osimertinib (Tagrisso)
3rd-generation EGFR TKI for EGFR-mutated NSCLC (exon 19 del or L858R). Superior CNS penetration; FLAURA trial OS benefit. Standard adjuvant therapy for resected stage IB-IIIA EGFR-mutated NSCLC (ADAURA trial).
Pembrolizumab (Keytruda) ± Chemotherapy
PD-1 inhibitor. First-line for PD-L1 ≥50% without driver mutations (KEYNOTE-024). Combined with carboplatin/pemetrexed (non-squamous) or carboplatin/paclitaxel+nab-paclitaxel (squamous) for PD-L1 any/unknown.
Alectinib (Alecensa)
2nd-generation ALK inhibitor for ALK-positive NSCLC. Superior to crizotinib and first-generation ALK TKIs. Excellent CNS penetration. ALEX trial established as frontline standard.
Sotorasib (Lumakras)
First-in-class KRAS G12C inhibitor (CodeBreaK 100 trial). For KRAS G12C-mutated NSCLC after ≥1 prior therapy. ~28% ORR.
Docetaxel ± Ramucirumab or Nintedanib
Standard second-line chemotherapy after immunotherapy/targeted therapy failure. Ramucirumab (anti-VEGFR2) adds modest benefit in REVEL trial. Nintedanib (adenocarcinoma, LUME-Lung 1).
Smoking cessation at any stage improves treatment outcomes and reduces second primary cancer risk
Low-dose CT (LDCT) lung cancer screening annually for high-risk patients (ages 50–80, ≥20 pack-year history, current or former smoker within 15 years)
Radon testing in home environment; mitigation if >4 pCi/L
Pulmonary rehabilitation to improve exercise capacity and quality of life
Nutritional support: maintain adequate protein intake, manage cancer cachexia
Bone-protective agents (zoledronic acid, denosumab) for bone metastases
Brain metastasis symptom monitoring: headache, confusion, weakness, seizures
Advance care planning discussions early in metastatic disease management
Prognosis
5-year survival: Stage I: 70–90% (resected); Stage II: 30–60%; Stage III: 15–35%; Stage IV: 6–8% (unselected). However, patients with oncogene-addicted NSCLC (EGFR, ALK, ROS1) treated with targeted therapy have median OS of 3–5 years in the metastatic setting. Patients with high PD-L1 (≥50%) treated with pembrolizumab have 5-year OS ~32%. Osimertinib adjuvant therapy reduces recurrence by ~80% in resected EGFR-mutated NSCLC. The field continues to evolve rapidly.
Non-Small Cell Lung Cancer is a medical condition classified under Oncology. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, representing approximately 85% of all lung cancer cases. Lung cancer remains the leading cause of cancer death in the United States, with approximately 238,000 new cases and 127,000 deaths annually. The field has been transformed by molecular profiling and immunotherapy, dramatically improving outcomes in selected patients. Understanding Non-Small Cell Lung Cancer is essential for patients, families, and healthcare providers to ensure timely diagnosis, appropriate treatment, and optimal outcomes.
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