History and exam

Key diagnostic factors

common

cough

A new or persistent cough, especially in a current or former smoker, is suspicious and requires imaging of the chest.

Cough is present at diagnosis in over 50% of patients with lung cancer and may be secondary to postobstructive pneumonia, endobronchial tumor, or pleural effusion.[83]

dyspnea

Present at diagnosis in the majority of patients.

Possible causes include tumor obstruction of the airway, underlying chronic obstructive pulmonary disease, pneumonia, phrenic nerve paralysis, or a pleural effusion.

hemoptysis

Occurs in approximately 25% of patients.[83]

Although massive hemoptysis is rare, patients with lung cancer often cough up blood-tinged sputum. Hemoptysis in a smoker is suspicious for lung cancer.

chest and/or shoulder pain

Chest pain or discomfort is present in approximately 33% of patients.[83]

The lung is devoid of pain fibers. Therefore, most patients with chest pain have tumors invading the pleura or chest wall. However, even patients with early disease can present with chest discomfort. Shoulder pain is the most common symptom in patients with superior sulcus tumors.[5]

weight loss

Independent negative prognostic factor and should be specifically addressed. It is more common in patients with locally advanced or metastatic disease. Most clinical trials define clinically relevant weight loss as >5%.[84][85]

Other diagnostic factors

common

male sex

Age-adjusted incidence (Surveillance, Epidemiology, and End Results Program 2017-2021) of lung cancer is higher in males than in females (54.9 new cases per 100,000 vs. 44.8 cases per 100,000, respectively).[7]

fatigue

Nonspecific symptom of lung cancer, and is often multifactorial.

pulmonary exam abnormalities

Auscultation of the lungs may demonstrate wheeze, rales, decreased breath sounds, and dullness to percussion.

uncommon

hoarseness

Between 2% and 18% of cases can present with hoarseness secondary to recurrent laryngeal nerve paralysis.[83]

confusion

A common symptom of brain metastases and electrolyte disturbances such as hypercalcemia and hyponatremia. Up to 25% of patients with lung cancer develop brain metastases.[86]

personality changes

Strongly suspicious of brain metastases in those affected with lung cancer.

nausea and vomiting

May indicate brain metastases.

headache

May indicate brain metastases.

dysphagia

May occur if the tumor itself or enlarged mediastinal lymph nodes have significantly impinged on the esophagus.

bone pain and/or fractures

Pain or pathologic fractures can result from bone metastases. The axial skeleton and proximal long bones are most frequently involved.[83]

weakness, paresthesias, and/or pain in C8/T1 distribution

Superior sulcus tumors can invade the brachial plexus causing weakness and/or atrophy of the intrinsic muscles of the hand, and paresthesias and/or pain in a C8/T1 distribution.

seizures

A common symptom of brain metastases.

cervical or supraclavicular adenopathy

The most common sites of regional spread are the hilum and mediastinum. The next echelon of lymph node spread is the supraclavicular fossa and cervical chains. In a proportion of cases the supraclavicular lymphadenopathy is impalpable, but detectable by ultrasound examination of the neck.[70]

Horner syndrome

Triad of ptosis, miosis, and ipsilateral anhidrosis occurs most frequently in patients with superior sulcus tumors, which can invade the sympathetic plexus.

facial swelling

May indicate compression of the superior vena cava, either from mediastinal adenopathy or from a right upper lobe tumor extending centrally into the mediastinum.

dilated neck or chest/abdominal wall veins

Distended neck veins or venous collaterals on the chest or abdominal wall may indicate compression of the superior vena cava.

finger clubbing

More common in non-small-cell lung cancer than in small cell lung cancer.[87]

hypertrophic pulmonary osteoarthropathy

Painful arthropathy of the wrists, ankles, and knees with periosteal new bone formation. Although rare, it is more common in cases of adenocarcinoma.

Risk factors

strong

cigarette smoking

Tobacco exposure continues to be the most important cause of lung cancer, and in the US and Europe up to 90% of lung cancer is directly attributable to smoking.[11]

There are numerous epidemiologic studies linking lung cancer and cigarette smoking.[26][27][28]

Tobacco smoke contains multiple carcinogens including polynuclear aromatic hydrocarbons, aromatic amines, N-nitrosamines, and other organic and inorganic compounds.[12]

environmental tobacco exposure

Environmental tobacco smoke (secondhand smoke) is an important cause of lung cancer, and approximately 1% to 2% of lung cancer cases may be attributed to it.[29]

Systematic reviews and meta-analyses suggest that exposure to secondhand smoke may increase relative risk of lung cancer by approximately 25% to 30%.[30][31]​​​ ​

chronic obstructive pulmonary disease (COPD)

COPD is associated with increased risk for lung cancer. The excess risk remains when smoking history is corrected for.[32][33]​ COPD has been reported to be a risk factor for lung cancer in never smokers.[34][35]

Whether COPD is truly independent of smoking remains debatable, owing to the fact that smoking is such a strong factor and residual confounding may be the explanation.[36] Despite this, COPD (whether a marker of smoking or in part independent) is a strong risk factor for lung cancer.

family history

A history of lung cancer in a first-degree relative is associated with an approximate doubling of the risk, independent of the smoking history.[37] This relative risk is as high as fivefold where the cancers develop in first-degree relatives under the age of 60 years.

radon gas exposure

Lung cancer has also been linked to radon gas, a radioactive decay product of uranium.[13][14]

Case-control studies have associated both occupational (mining) and residential radon exposure to lung cancer. Radon may contribute up to an estimated 14% of all lung cancer cases.[38][39]​ This may increase where homes are made more energy efficient.[40]

older age

In the US, the median age of patients at diagnosis is 71 years.[7]

Less than 10% of cases are diagnosed before 55 years of age.[7]

weak

asbestos exposure

Occupational exposure to asbestos has been shown to confer some risk for lung cancer.[15][16]

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