Lung Cancer for USMLE Step 3

Lung Cancer for the USMLE Step 3 Exam

Lung Cancer Overview

Leading cause of cancer-related mortality in the U.S. and worldwide.
Primarily affects individuals over 50, with highest risk among smokers.
Increasing prevalence in women and nonsmokers due to rising adenocarcinoma rates.

Smoking: Principal risk, with a direct relationship to pack-years.
Environmental and Occupational Exposure: Radon, asbestos, secondhand smoke, air pollution.
Genetic Mutations: Mutations in genes like EGFR, ALK, and KRAS are associated with higher risk.
Underlying Lung Disease: Higher risk in patients with COPD or pulmonary fibrosis.

Types of Lung Cancer

Adenocarcinoma: Most common subtype, particularly in nonsmokers and women; often peripheral in location.

Squamous Cell Carcinoma: Strongly linked to smoking, usually central; often causes cavitation and hypercalcemia.
Large Cell Carcinoma: Rare, poorly differentiated, fast-growing, and can be central or peripheral.

Highly aggressive, rapidly metastatic, with strong associations with smoking.
Frequently presents with paraneoplastic syndromes, such as SIADH and ectopic ACTH production.

Clinical Presentation

Cough: Chronic and may be persistent or worsening.
Hemoptysis: More common in centrally located tumors.
Dyspnea: Due to airway obstruction, pleural effusion, or tumor burden.
Chest Pain: Persistent, often worsening with deep breathing, associated with pleural invasion.

Weight Loss and Anorexia: Common in advanced disease due to high metabolic demand.
Fatigue: Common, related to disease burden and potential anemia.

SIADH: Hyponatremia, more common in SCLC.
Cushing Syndrome: Due to ectopic ACTH production in SCLC.
Hypercalcemia: Often in squamous cell carcinoma due to PTH-related peptide.
Neurologic: Lambert-Eaton syndrome with proximal muscle weakness, associated with SCLC.

Diagnostic Evaluation

Chest X-ray: First-line test; may reveal a nodule, mass, or effusion.
Chest CT with Contrast: Essential for assessing tumor size, location, lymph node involvement, and metastasis.
PET-CT: Useful in staging and detection of metastases.

Sputum Cytology: Especially for centrally located tumors; limited sensitivity.
Bronchoscopy with Biopsy: Preferred for central tumors; allows direct visualization and biopsy.
CT-Guided Needle Biopsy: For peripheral lesions or when bronchoscopy is not feasible.

NSCLC Staging (TNM): Tumor size, lymph node involvement, and metastasis determine staging.
Stages I and II: Localized and potentially curable.
Stages III and IV: Advanced, generally requiring systemic therapy.
SCLC Staging: Limited (within one hemithorax) vs. extensive (beyond hemithorax or with distant metastasis).

Treatment

Surgery: Preferred in early-stage (I-II) disease without distant metastasis.
Radiation Therapy: Used for non-surgical candidates or as palliative therapy.
Chemotherapy: Platinum-based regimens, often used in advanced-stage disease.
Targeted Therapy and Immunotherapy: Indicated for advanced NSCLC with specific mutations (e.g., EGFR, ALK) or PD-L1 expression.

Chemotherapy: Primary treatment; often platinum-based (cisplatin or carboplatin).
Radiation Therapy: Commonly combined with chemotherapy for limited-stage disease.
Prophylactic Cranial Irradiation (PCI): Reduces risk of brain metastasis in responders to initial therapy.

Key Points

Lung cancer remains the leading cause of cancer-related death, with smoking as the primary risk factor.
NSCLC is most common, with adenocarcinoma frequently affecting nonsmokers and females; squamous cell carcinoma is often smoking-related.
SCLC is aggressive and highly associated with paraneoplastic syndromes (e.g., SIADH, Lambert-Eaton).
Initial diagnosis relies on imaging, with chest X-ray and CT as primary modalities; PET-CT aids in staging.
Treatment is stage-dependent:

NSCLC may be treated with surgery, radiation, chemotherapy, and targeted or immunotherapy based on molecular markers.
SCLC treatment centers on chemotherapy and radiation, with PCI for limited-stage cases.