Lung Cancer for USMLE Step 1
Lung Cancer for the USMLE Step 1 Exam
Lung Cancer Overview
- Epidemiology:
- Most common cause of cancer death worldwide.
- Primarily affects adults over 50, with strong associations with smoking.
- Higher prevalence in males, but increasing in females.
- Risk Factors:
- Tobacco Use: Principal risk, with direct correlation to duration and intensity of smoking.
- Environmental Factors: Secondhand smoke, radon, asbestos, air pollution.
- Genetic Mutations: Mutations in EGFR, ALK, and KRAS genes contribute to tumorigenesis.
- Personal History: Higher risk if there’s a history of COPD, fibrosis, or prior radiation therapy to the chest.
Types of Lung Cancer
- Non-Small Cell Lung Cancer (NSCLC):
- Accounts for ~85% of cases.
- Adenocarcinoma: Most common type, especially in nonsmokers; peripheral lung location.
- Squamous Cell Carcinoma: Strongly linked to smoking; central location, often with cavitation.
- Large Cell Carcinoma: Less common, poorly differentiated, usually peripheral, and fast-growing.
- Small Cell Lung Cancer (SCLC):
- Comprises ~15% of lung cancers.
- Strongly linked to smoking; central location.
- Rapidly progressive and often presents with paraneoplastic syndromes (e.g., SIADH, ACTH secretion).
Pathophysiology
- Oncogenic Mutations:
- Genetic mutations (e.g., EGFR, ALK, KRAS) trigger uncontrolled cell growth and transformation.
- Tumor suppressor gene inactivation (e.g., TP53) and oncogene activation contribute to tumor progression.
- Tumor Growth and Spread:
- Local Invasion: Tumor spreads within lung tissue, bronchi, and possibly chest wall.
- Lymphatic Spread: Common in advanced stages, often involving mediastinal nodes.
- Distant Metastasis: Typical sites include liver, brain, bones, and adrenal glands.
Clinical Presentation
- Primary Symptoms:
- Cough: Persistent, worsens over time, especially with centrally located tumors.
- Hemoptysis: Especially in tumors invading bronchi.
- Dyspnea: From tumor obstruction, pleural effusion, or extensive lung involvement.
- Chest Pain: Due to pleural or chest wall invasion.
- Systemic Symptoms:
- Weight Loss: Unintentional, often due to increased metabolic activity of cancer cells.
- Fatigue: Common in advanced disease.
- Paraneoplastic Syndromes:
- SIADH: Common in SCLC, leading to hyponatremia.
- Cushing Syndrome: Due to ectopic ACTH production, seen in SCLC.
- Hypercalcemia: Most common in squamous cell carcinoma due to PTH-related peptide production.
Diagnostic Evaluation
- Imaging:
- Chest X-ray: Initial test; may reveal a mass, nodule, or pleural effusion.
- CT Scan: Essential for characterizing tumor size, location, and lymph node involvement.
- Biopsy and Cytology:
- Sputum Cytology: Helpful for central tumors.
- Bronchoscopy: Useful for centrally located tumors; allows direct visualization and biopsy.
- CT-Guided Biopsy: For peripheral lesions, performed under imaging guidance.
Staging and Classification
- NSCLC Staging (TNM):
- Based on tumor size (T), lymph node involvement (N), and metastasis (M).
- Early-stage disease (Stage I-II) has higher survival compared to advanced (Stage III-IV).
- SCLC Staging:
- Limited Stage: Confined to one hemithorax.
- Extensive Stage: Spread beyond the hemithorax or distant metastasis.
Treatment Overview
- NSCLC Treatment:
- Surgery: Preferred in early stages, including lobectomy or segmentectomy.
- Chemotherapy and Radiation: For advanced disease or as adjuvant/neoadjuvant therapy.
- Targeted Therapy: For patients with specific mutations (e.g., EGFR, ALK inhibitors).
- SCLC Treatment:
- Chemotherapy: Main treatment, usually platinum-based (cisplatin or carboplatin).
- Radiation Therapy: Often concurrent with chemotherapy in limited-stage disease.
Key Points
- Lung cancer is the most common cause of cancer mortality, with NSCLC and SCLC as the main types.
- Smoking is the most significant risk factor; other risk factors include environmental exposures and genetic mutations.
- Adenocarcinoma is the most common lung cancer in nonsmokers and females, typically presenting peripherally.
- SCLC is highly aggressive, often presenting with paraneoplastic syndromes and has poor prognosis.
- Diagnosis involves imaging and biopsy, with CT scan and bronchoscopy as key modalities.
- Treatment varies by stage: NSCLC may involve surgery, chemotherapy, and targeted therapies, while SCLC is primarily treated with chemotherapy and radiation.