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Patients who present with suspected lung cancer require a detailed clinical evaluation followed by noninvasive testing and invasive procedures to establish both the histopathologic diagnosis as well as disease stage. Historically, great emphasis has been placed upon the differentiation of small-cell lung cancer (SCLC) from non–small-cell lung cancer (NSCLC). SCLC, which accounts for 13% of bronchogenic carcinomas, is histologically and clinically distinct from NSCLC.1 NSCLCs comprise clinically, pathologically, and molecularly diverse tumors that respond to different therapeutic agents based on specific histologic phenotypes and molecular characteristics.

The clinician evaluating the patient with suspected lung cancer must take into account several factors, including the likelihood of SCLC versus NSCLC, probability of metastatic disease, comorbid illness, functional status, presence of paraneoplastic syndromes, and treatment preferences of the patient. Good decision-making regarding appropriate diagnostic test selection must incorporate (1) careful assessment of pretest probabilities based upon clinical evaluation and initial radiographic features, and (2) understanding of specific test characteristics. The main objectives of the diagnostic and clinical staging evaluation are to obtain adequate tissue to establish the histopathologic diagnosis and, when indicated, molecular and diagnostic biomarker testing screening for actionable oncogenic driver mutations and programmed death ligand 1(PD-L1) expression, and to ascertain the extent of disease to determine candidacy for specific therapies. These twinned goals should be accomplished in the safest, least invasive, and most cost-effective manner possible.


A detailed history and physical examination are of key importance in the assessment of the patient’s overall health status and medical appropriateness for specific therapies.2 Certain comorbid conditions may reduce therapeutic options. Limited cardiopulmonary reserve may preclude surgical intervention. A thorough history can also assist a physician in determining the overall extent of disease. At the time of presentation, it is most useful to consider the clinical stage using the International Association for the Study of Lung Cancer (IASLC) 8th edition of the tumor, node, and metastasis (TNM) classification system (Table 112-1); pathologic stage is established only after surgical resection.3

TABLE 112-1TNM Staging System for Lung Cancer

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