Approach
Persistent cough associated with hemoptysis or weight loss in a smoker over the age of 50 years are key features that should alert the clinician to the possibility of lung cancer. However, lung cancer can present without symptoms as an incidental mass on chest x-ray or computed tomography (CT).
History
Symptoms of a primary tumor include cough, hemoptysis, chest pain, and/or dyspnea. Some patients may present with hoarseness, secondary to recurrent laryngeal nerve paralysis. Patients may also present with nonspecific symptoms, such as weight loss or fatigue.
Smoking history, the use of alternative tobacco and nicotine delivery products (e.g., e-cigarettes and vaping products), nutritional status, and performance status (an objective assessment of the patient's ability to perform activities of daily living) should be specifically addressed.
Many patients have distant metastasis at the time of presentation. The most frequent sites of distant metastasis are the lungs, liver, brain, bone, and adrenal glands. Symptoms depend on the sites and extent of involvement. Pain or fractures can develop as a result of bone metastasis. Lung cancer is the most common cause of brain metastasis.[29] Common symptoms of brain metastases include confusion, personality change, seizures, weakness, focal neurologic deficits, nausea and vomiting, and headaches.
Physical exam
The general appearance of the patient is important. The patient may appear ill, short of breath, and have evidence of recent weight loss. The neck and supraclavicular fossae should be carefully examined for adenopathy. Finger clubbing and hypertrophic osteoarthropathy may be present but are less common in SCLC compared with non-small cell lung cancer.[4]
Although the pulmonary exam is normal in some patients with early lung cancer, many present with one or more findings during auscultation. The following signs are common:
Wheezing from underlying COPD or bronchial obstruction
Rales due to postobstructive pneumonia or atelectasis
Diminished breath sounds from bronchial obstruction, pleural effusion, and/or COPD.
Pleural effusions can be assessed with percussion of the lung fields, showing a characteristic dullness.
Facial and upper extremity swelling, distended neck veins, and dilated collateral vessels on the chest or abdominal wall may indicate compression of the superior vena cava.
Paraneoplastic manifestations of SCLC that may be clinically apparent include Cushing syndrome from ectopic adrenocorticotropic hormone secretion and neurologic manifestations of myopathy and sensory neuropathy.
Investigations
A chest x-ray and CT of the chest and upper abdomen are standard and help define the primary tumor and evaluate for regional spread.
A standard posteroanterior and lateral chest x-ray is an inexpensive and simple initial step to evaluate cough, chest pain, and/or hemoptysis.
A new abnormality on chest x-ray should be further assessed with CT. A chest CT should also be obtained in patients, especially smokers, with concerning symptoms and a normal chest x-ray.
Pathologic confirmation of disease is essential before treatment can commence. The choice of which test is used to gain a tissue sample depends on the location of the lesion to be biopsied. If distant metastatic disease is suspected on imaging, biopsy of metastatic lesion is recommended in order to confirm stage at the time of biopsy.
Procedures for biopsy of lung lesions include flexible bronchoscopy and transthoracic needle aspiration biopsy:
Bronchoscopy is performed when CT abnormalities (i.e., a mass or adenopathy) are accessible to the bronchoscope. It is also used to assess new and/or unexplained pulmonary symptoms (i.e., hemoptysis, wheezing, cough). Flexible bronchoscopy requires conscious sedation. During the procedure, the tracheobronchial tree is carefully examined. Endobronchial tumors can be biopsied. Washings, brushings, and bronchoalveolar lavage are performed. Suspicious parenchymal lesions and mediastinal lymph nodes that are accessible can also be biopsied.[30]
Transthoracic needle aspiration biopsy is often necessary for peripheral lesions that are inaccessible to bronchoscopy. If a pleural effusion exists, thoracentesis collects cells for cellular evaluation of malignancy. Ultrasound guidance is helpful for small effusions.
Method of biopsy for metastatic sites depends on the anatomic location and least invasive approach.[31]
After a pathologic diagnosis has been obtained, further staging studies guide appropriate treatment. All patients should be evaluated for brain metastases, ideally with a magnetic resonance imaging scan.[5][31]
Positron emission tomography (PET)-CT can confirm the extent of intrathoracic disease and identify distant metastases; fluorodeoxyglucose (FDG)-PET/CT scan is superior to PET alone.[5] PET-CT can also be performed prior to tissue sampling in order to identify possible metastatic lesion(s) that can be biopsied, determining stage and confirming pathologic diagnosis in the same procedure.
Bone scan can detect bone metastasis. However, if staging with PET-CT is performed, bone scan is unnecessary as PET-CT is more accurate.[5]
If a pleural effusion is present, it should be evaluated by thoracentesis or thoracoscopy.[5]
Bone marrow aspiration may be indicated if there are nucleated red cells in the peripheral smear, or unexplained anemia or thrombocytopenia.[5][31]
Mediastinoscopy is performed to determine node status in patients with a solitary pulmonary mass without radiographic evidence of lymphadenopathy, as these patients may be candidates for surgery.[5]
Ancillary studies
A complete blood count, chemistry panel, and liver function tests, including alkaline phosphatase, should be performed in all patients as baseline tests before initiation of treatment and to detect paraneoplastic syndromes.[5][31] Examples of paraneoplastic syndromes that are detected by laboratory screening include syndrome of inappropriate antidiuretic hormone (hyponatremia), Cushing syndrome (hyperglycemia, hypokalemia), and cancer-related anemia. In metastatic disease, alkaline phosphatase levels can be elevated, indicating potential bone metastases.[5]
All lung cancer patients anticipated to receive chest radiation therapy or surgery should have pulmonary function tests, including forced expiratory volume in the first second of expiration (FEV₁) and diffusion capacity of lung for carbon monoxide (DLCO).[31][32][33]
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