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Lung Cancer for ABIM

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Lung Cancer for the American Board of Internal Medicine Exam
Epidemiology of Lung Cancer
  • Prevalence and Mortality:
    • Leading cause of cancer-related death worldwide.
    • Accounts for ~25% of all cancer deaths in the U.S., more than colon, breast, and prostate cancers combined.
    • Five-year survival rate ~20%, highly stage-dependent.
  • Risk Factors:
    • Tobacco Use: Primary risk factor, responsible for ~85% of cases. Risk increases with the number of pack-years.
    • Secondhand Smoke: Contributes to increased risk, especially in nonsmokers.
    • Environmental and Occupational Exposures: Radon, asbestos, air pollution, and certain chemicals (e.g., arsenic) increase risk.
    • Genetic Factors: Family history and certain genetic mutations (e.g., EGFR, ALK, KRAS) predispose individuals to lung cancer.
    • Age and Gender: Higher prevalence in older adults and in men, though rates among women are rising.
Pathophysiology
  • Tumor Origin:
    • Develops from epithelial cells in the bronchi or alveoli.
    • Genetic Mutations: Key mutations in tumor suppressor genes (e.g., TP53) and oncogenes (e.g., EGFR, ALK, KRAS) drive tumor growth and proliferation.
    • Histologic Transformation: Normal cells undergo hyperplasia, metaplasia, dysplasia, and eventually neoplasia.
  • Mechanisms of Spread:
    • Local Invasion: Tumor infiltrates surrounding lung tissue, pleura, chest wall, or mediastinal structures.
    • Lymphatic Spread: Metastasis to regional lymph nodes, which is common in advanced stages.
    • Hematogenous Spread: Dissemination to distant organs, especially liver, brain, bones, and adrenal glands.
Types of Lung Cancer
  • Non-Small Cell Lung Cancer (NSCLC) (~85% of cases):
    • Adenocarcinoma (~40% of lung cancers): Most common subtype, especially in nonsmokers and women.
    • Peripheral lung location; often presents with metastasis to brain, bone, or liver.
Adenocarcinoma Lung Cancer
    • Squamous Cell Carcinoma (~25-30%): Linked to smoking; typically central in location with cavitation.
    • Tends to cause obstructive symptoms (e.g., post-obstructive pneumonia).
    • Large Cell Carcinoma (~10-15%): Poorly differentiated, often peripheral, with a rapid growth rate.
  • Small Cell Lung Cancer (SCLC) (~15% of cases):
    • Highly aggressive, typically central in location with rapid growth and early metastasis.
    • Strongly associated with smoking.
    • Often associated with paraneoplastic syndromes, including SIADH and ACTH production.
Clinical Presentation
  • Respiratory Symptoms:
    • Cough: Most common presenting symptom; chronic and may worsen over time.
    • Hemoptysis: Can be seen in centrally located tumors or those causing bronchial erosion.
    • Dyspnea: Due to airway obstruction, pleural effusion, or lung parenchymal involvement.
    • Chest Pain: Often from pleural or chest wall invasion; typically dull and persistent.
  • Systemic Symptoms:
    • Weight Loss and Anorexia: Common in advanced disease due to metabolic demands of the tumor.
    • Fatigue: Due to anemia, infection, or tumor burden.
  • Paraneoplastic Syndromes:
    • Endocrine: SIADH (especially in SCLC), hypercalcemia (typically squamous cell carcinoma), and Cushing syndrome.
    • Neurologic: Lambert-Eaton syndrome (proximal muscle weakness in SCLC).
    • Skeletal: Hypertrophic osteoarthropathy leading to joint pain and clubbing.
Diagnostic Evaluation
  • Imaging:
    • Chest X-ray: Initial modality; may reveal a solitary nodule, mass, or mediastinal widening.
    • CT Scan: More sensitive, helps assess tumor size, lymph node involvement, and metastasis.
    • PET Scan: Useful for staging by detecting metabolic activity in lymph nodes and distant metastasis.
  • Biopsy Techniques:
    • Bronchoscopy with Biopsy: For centrally located tumors.
    • CT-Guided Needle Biopsy: For peripheral lung lesions.
    • Surgical Biopsy: Video-assisted thoracic surgery (VATS) or open biopsy if other methods are inconclusive.
  • Laboratory Studies:
    • Sputum Cytology: Simple, non-invasive test with higher yield in centrally located tumors.
    • Blood Tests: Can include tumor markers (e.g., carcinoembryonic antigen in adenocarcinoma), though not routinely recommended for diagnosis.
Staging
  • NSCLC Staging (TNM System):
    • T (Tumor): Size and extent of the primary tumor.
    • N (Node): Regional lymph node involvement.
    • M (Metastasis): Presence or absence of distant metastasis.
    • Stages I-IV, with Stage I being localized and Stage IV indicating distant spread.
  • SCLC Staging:
    • Limited Stage: Confined to one hemithorax and regional lymph nodes; potentially curable with chemotherapy and radiation.
    • Extensive Stage: Metastasis beyond one hemithorax; generally treated with palliative intent.
Treatment
  • NSCLC Treatment:
    • Surgery: Preferred for early-stage (Stage I-II) tumors with no metastasis; options include lobectomy, pneumonectomy, or segmentectomy.
    • Radiation Therapy: Used in patients who are not surgical candidates or for advanced disease.
    • Chemotherapy: Platinum-based regimens (e.g., cisplatin, carboplatin) for advanced-stage disease.
    • Targeted Therapy: For specific mutations (e.g., EGFR inhibitors, ALK inhibitors).
    • Immunotherapy: Checkpoint inhibitors (e.g., pembrolizumab) for advanced disease, especially in high PD-L1 expression.
  • SCLC Treatment:
    • Chemotherapy: Platinum-based (e.g., cisplatin or carboplatin with etoposide) as the mainstay of treatment.
    • Radiation: Often concurrent with chemotherapy in limited-stage disease.
    • Prophylactic Cranial Irradiation (PCI): Reduces the risk of brain metastasis in SCLC patients who respond to initial treatment.
Prognosis
  • NSCLC:
    • Prognosis varies by stage: ~60-80% five-year survival for Stage I, but <5% for Stage IV.
    • Molecular characteristics (e.g., EGFR, ALK) impact survival and response to targeted therapies.
  • SCLC:
    • Poor prognosis due to early metastasis; median survival 15-20 months for limited-stage, 8-13 months for extensive-stage.
    • Most patients relapse despite initial response to therapy.
Key Points
  • Lung cancer is the leading cause of cancer-related mortality, with NSCLC accounting for 85% and SCLC 15% of cases.
  • Tobacco use is the primary risk factor, with other risks including secondhand smoke, radon, asbestos, and genetic mutations.
  • NSCLC subtypes include adenocarcinoma, squamous cell carcinoma, and large cell carcinoma, each with unique clinical features.
  • SCLC is highly aggressive and often presents with paraneoplastic syndromes, such as SIADH and Lambert-Eaton syndrome.
  • Staging is essential for treatment planning:
    • NSCLC is staged using the TNM system, while SCLC has limited and extensive stages.
  • Treatment modalities for NSCLC include surgery, radiation, chemotherapy, targeted therapy, and immunotherapy, tailored by stage.
  • SCLC is primarily treated with chemotherapy and radiation, with prophylactic cranial irradiation for limited-stage responders.
  • Prognosis varies significantly by type and stage; NSCLC has a better overall survival rate, especially in early stages.
  • Early detection through screening (e.g., low-dose CT in high-risk patients) is critical to improve outcomes.

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