Clinical manifestations of lung cancer

INTRODUCTION — Worldwide, lung cancer occurred in approximately 2.2 million patients in 2020 and caused an estimated 1.8 million deaths [1]. In the United States, lung cancer occurs in approximately 235,000 patients and causes over 130,000 deaths annually [2].

Around 1953, lung cancer became the most common cause of cancer deaths in men, and in 1985, it became the leading cause of cancer deaths in women. However, lung cancer deaths have begun to decline in both men and women, reflecting a decrease in smoking. (See "Females and lung cancer".)

The majority of patients with lung cancer have advanced disease at clinical presentation. This may reflect the aggressive biology of the disease and the frequent absence of symptoms until locally advanced or metastatic disease is present. High-risk patients may be diagnosed while asymptomatic through screening with low-dose computed tomography.

Symptoms may result from local effects of the tumor, from regional or distant spread, or from distant effects not related to metastases (paraneoplastic syndromes). Approximately three-fourths of nonscreened patients have one or more symptoms at the time of diagnosis. One study noted that the most common symptoms at presentation were cough (55 percent), dyspnea (45 percent), pain (38 percent), and weight loss (36 percent) (table 1) [3].

This discussion will present the clinical manifestations of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Screening and risk factors for lung cancer, as well as an overview of the initial evaluation, diagnosis, treatment, and prognosis of lung cancer are presented separately. A more detailed discussion on risk factors is also presented elsewhere.

●(See "Screening for lung cancer".)

●(See "Cigarette smoking and other possible risk factors for lung cancer".)

●(See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer".)

●(See "Overview of the initial treatment and prognosis of lung cancer".)

INTRATHORACIC CLINICAL MANIFESTATIONS — There are a wide range of symptoms due to the intrathoracic effects of the cancer, the most common of which are cough, hemoptysis, chest pain, and dyspnea.

Cough — The new onset of cough in a smoker or former smoker should raise suspicion for lung cancer.

Cough is present in 50 to 75 percent of lung cancer patients at presentation and occurs most frequently in patients with squamous cell and small cell carcinomas because of their tendency to involve central airways [3-5]. Bronchorrhea or cough productive of large volumes of thin, mucoid secretions may be a feature of mucinous adenocarcinoma and usually indicates advanced disease. Both NSCLC and SCLC may cause a postobstructive pneumonia. However, bronchiectasis from bronchial obstruction is uncommon because lung cancer usually progresses too rapidly for bronchiectasis to develop. By contrast, slow-growing neoplasms such as carcinoid tumor or hamartoma are more likely to present with bronchiectasis. (See "Causes and epidemiology of subacute and chronic cough in adults" and "Lung neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging" and "Pathology of lung malignancies", section on 'Adenocarcinoma'.)

The presenting symptom has some bearing on prognosis; a series of 3800 patients with lung cancer showed that patients presenting with cough had a better prognosis than those presenting with other symptoms [6]. Presentation with cough appeared to correlate with earlier stage, and possibly serendipitous discovery of the cancer.

Hemoptysis — In a patient with hemoptysis, the likelihood of lung cancer varies from 3 to 34 percent in different series depending upon the patient's age and smoking history [7]. In smokers with hemoptysis and a nonsuspicious or normal chest radiograph, bronchoscopy will diagnose lung cancer in approximately 5 percent of cases [8]. (See "Evaluation of nonlife-threatening hemoptysis in adults" and "Evaluation and management of life-threatening hemoptysis".)

Hemoptysis is reported by 15 to 30 percent of patients who are diagnosed with lung cancer, although bronchitis is the most common cause of this symptom [3-5]. Any amount of hemoptysis can be alarming to the patient, and large volumes of hemoptysis may cause asphyxia.

Chest pain — Chest pain is present in approximately 20 to 40 percent of patients presenting with lung cancer [3,5,9]. It can be quite variable in character and is more common in younger compared with older patients. Pain is typically present on the same side of the chest as the primary tumor. Dull, aching, persistent pain may occur from mediastinal, pleural, or chest wall extension, but the presence of pain does not necessarily preclude resectability. Although pleuritic pain may be the result of direct pleural involvement, obstructive pneumonitis or a pulmonary embolus related to a hypercoagulable state may also cause chest pain.

Dyspnea — Shortness of breath is a common symptom in patients with lung cancer at the time of diagnosis, occurring in approximately 25 to 40 percent of cases [3-5]. Dyspnea may be due to extrinsic or intraluminal airway obstruction, obstructive pneumonitis or atelectasis, lymphangitic tumor spread, tumor emboli, pneumothorax, pleural effusion, or pericardial effusion with tamponade. Partial obstruction of a bronchus may cause a localized wheeze, heard by the patient or by the clinician on auscultation, while stridor can result from obstruction of the trachea.

Pulmonary function testing may be useful in a patient with dyspnea due to lung cancer, as it may show flattening of the expiratory and/or inspiratory flow-volume loop from presence of tumor in the trachea itself (figure 1), from extrinsic compression, or from vocal cord paralysis. (See "Overview of pulmonary function testing in adults".)

Unilateral paralysis of the diaphragm may be due to damage of the phrenic nerve (image 1). Patients may be asymptomatic or report shortness of breath. In one series, lung cancer was the most common neoplasm affecting the phrenic nerve, although malignancy accounted for only 4 percent of patients presenting with diaphragmatic paralysis [10]. (See "Diagnostic evaluation of adults with bilateral diaphragm paralysis".)

Hoarseness — The differential diagnosis of persistent hoarseness in a smoker includes both laryngeal cancer and lung cancer. In patients with lung cancer, this is due to malignancy involving the recurrent laryngeal nerve along its course under the arch of the aorta and back to the larynx [11,12]. (See "Hoarseness in adults" and "Overview of the diagnosis and staging of head and neck cancer".)

Pleural involvement — Pleural involvement can manifest as pleural thickening or nodularity without pleural effusion (image 2) or as malignant pleural effusion.

Although malignant pleural effusions can cause dyspnea and cough, approximately one-fourth of patients who have lung cancer and pleural metastases are asymptomatic [13]. Although a malignant pleural effusion precludes curative resection, not all pleural effusions in patients with lung cancer are malignant. A benign pleural effusion may occur in a patient with a resectable lung cancer due to lymphatic obstruction, postobstructive pneumonitis, or atelectasis. In a patient with a pleural effusion, the presence of tumor needs to be confirmed or excluded so that a chance for curative resection is not missed. Series report that 5 to 14 percent of patients with NSCLC and an ipsilateral pleural effusion have resectable disease [14,15]. Surgical thoracoscopy or medical pleuroscopy should follow two negative pleural fluid cytologies to further evaluate the pleural space prior to surgical resection of a primary lesion.

Malignant effusions are typically exudates and may be serous, serosanguineous, or grossly bloody. The yield of pleural fluid cytology after a single thoracentesis in patients with documented pleural involvement is approximately 60 percent; the yield rises to approximately 75 percent with a second thoracentesis, and there is little additional gain with additional thoracentesis [16,17]. Closed pleural biopsy adds little to the yield of cytologic examination. In a patient with a suspected malignancy, repeat pleural fluid cytology with or without pleural biopsy is appropriate if the initial study is negative. A prospective series evaluated cytologic yield from pleural fluid aliquots of 10 mL, 60 mL, and ≥150 mL [18]. The sensitivity for diagnosing malignancy in the pleural fluid was lower for volumes of 10 mL compared with the higher volumes. Medical pleuroscopy has a sensitivity of >90 percent for malignancy and may be considered for patients with pleural effusions and suspected malignancy who are cytology negative (picture 1) [19]. (See "Pleural fluid analysis in adults with a pleural effusion".)

During the course of their disease, approximately 10 to 15 percent of patients who have lung cancer will have a malignant pleural effusion (image 3A-B) [20]. The management of patients with malignant pleural effusions is discussed separately. (See "Management of malignant pleural effusions".)

Superior vena cava syndrome — Obstruction of the superior vena cava (SVC) causes symptoms that commonly include a sensation of fullness in the head and dyspnea. Cough, pain, and dysphagia are less frequent. Physical findings include dilated neck veins; a prominent venous pattern on the chest; edema of the face, neck, and upper extremities; and a plethoric appearance (picture 2). The chest radiograph typically shows widening of the mediastinum or a right hilar mass. Computed tomography can often identify the cause, level of obstruction, and extent of collateral venous drainage [21].

The SVC syndrome is more common in patients with SCLC than NSCLC. For most patients who have SVC syndrome secondary to lung cancer, the symptoms resolve after treatment of the mediastinal tumor. The pathophysiology and treatment options for the management of patients with SVC syndrome are discussed separately. (See "Malignancy-related superior vena cava syndrome".)

Pancoast syndrome — Lung cancers arising in the superior sulcus cause a characteristic Pancoast syndrome manifested by pain (usually in the shoulder, and less commonly in the arm, scapula, and fingers), Horner syndrome, bony destruction, and atrophy of hand muscles. (See "Horner syndrome".)

Pancoast syndrome is most commonly caused by NSCLC (typically squamous cell) and only rarely by SCLC (image 4A-B). The presentation, diagnosis, and treatment of patients with Pancoast syndrome due to superior sulcus tumors is discussed in detail elsewhere. (See "Superior pulmonary sulcus (Pancoast) tumors".)

CLINICAL MANIFESTATIONS OF EXTRATHORACIC METASTASES — Lung cancer can spread to any part of the body. Metastatic spread may result in the presenting symptoms or may occur later in the course of disease.

The staging at presentation of patients with known or suspected lung cancer is reviewed elsewhere. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Tumor, node, metastasis (TNM) staging system for lung cancer".)

The most frequent sites of distant metastasis are the liver, adrenal glands, bones, and brain.

Bone — Metastasis from lung cancer to bone is frequently symptomatic. Pain in the back, chest, or extremity and elevated levels of serum alkaline phosphatase are usually present in patients who have bone metastasis. The serum calcium may be elevated due to extensive bone disease. Approximately 20 percent of patients with NSCLC have bone metastases on presentation [22]. An osteolytic radiographic appearance is more frequent than an osteoblastic one, and the most common sites of involvement are the vertebral bodies (image 5 and image 6). Bone metastases are even more frequent in SCLC and can be found in 30 to 40 percent of patients [23]. Positron emission tomography (PET) and integrated PET with computed tomography(CT; PET-CT) have improved the ability to identify metastases to many organs, including bone, with greater sensitivity than CT or bone scan [24]. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Clinical-directed imaging'.)

The use of osteoclast inhibitors in patients with bone metastases from solid tumors is discussed separately. (See "Osteoclast inhibitors for patients with bone metastases from breast, prostate, and other solid tumors", section on 'Indications for osteoclast inhibitor therapy'.)

Adrenal — The adrenal glands are a frequent site of metastasis, occurring in 40 percent in one autopsy series [25], but such metastases are only rarely symptomatic. Occasionally, patients with an adrenal metastasis will have localized symptoms (eg, back or abdominal pain) if the tumor is large or rapidly growing or has caused a retroperitoneal hemorrhage [26]. Adrenal metastases do not usually result in adrenal insufficiency unless both adrenal glands are significantly (>90 percent) consumed by disease. In these rare instances, patients can present with loss of appetite, weight loss, nausea, abdominal pain, weakness, and electrolyte imbalances secondary to adrenal insufficiency.

Concern about adrenal metastasis usually occurs when a unilateral mass is found by staging CT in a patient with a known or suspected lung cancer. Only a fraction of adrenal masses detected on staging scans represent metastasis. This was illustrated by a series of 330 patients with operable NSCLC, in which 32 (10 percent) had an isolated adrenal mass [27]. Only 8 of these 32 (25 percent) were malignant, while the remainder had benign lesions (adenomas, nodular hyperplasia, hemorrhagic cysts). Conversely, a negative imaging study does not exclude adrenal metastases. A study of patients with SCLC found that 17 percent of adrenal biopsies showed metastatic involvement despite having a normal CT scan [28].

The lack of specificity of an initial CT identifying an adrenal mass creates a special problem in patients with an otherwise resectable lung cancer. In this situation, PET may be particularly useful in distinguishing a benign from malignant adrenal mass (figure 2) [29]. Other procedures that may be useful in excluding a metastasis include magnetic resonance imaging consistent with a benign adenoma or a negative needle biopsy. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Clinical-directed imaging'.)

Brain — Neurologic manifestations of lung cancer include metastases and paraneoplastic syndromes. (See 'Paraneoplastic phenomena' below.)

Symptoms from central nervous system metastasis are similar to those with other tumors and include headache, vomiting, visual field loss, hemiparesis, cranial nerve deficit, and seizures. (See "Epidemiology, clinical manifestations, and diagnosis of brain metastases".)

In patients with NSCLC, the frequency of brain metastasis is greatest with adenocarcinoma and least with squamous cell carcinoma. The risk for brain metastasis increases with larger primary tumor size and the presence of regional node involvement (image 7) [30]. For carefully selected patients, sequential resection may be feasible in cases that have operable NSCLC in the chest and a solitary brain metastasis. (See "Overview of the treatment of brain metastases".)

In patients with SCLC, metastasis to brain is present in approximately 20 to 30 percent of patients at presentation [31]. Without prophylactic irradiation, relapse in the brain occurs in approximately one-half of patients within two years. Randomized trials have shown that the frequency of brain metastases can be significantly reduced with prophylactic cranial radiation. (See "Prophylactic cranial irradiation for patients with small cell lung cancer".)

Liver — Symptomatic hepatic metastases are uncommon early in the course of disease. Asymptomatic liver metastases may be detected at presentation by liver enzyme abnormalities, CT (image 8), or PET (image 9). Among patients with otherwise resectable NSCLC in the chest, CT evidence of liver metastasis has been identified in approximately 3 percent of cases [32]. PET or integrated PET-CT identifies unsuspected metastases in the liver or adrenal glands in approximately 4 percent of patients [33,34]. The incidence of liver metastases is much higher later in the course of the disease. Autopsy studies have shown that hepatic metastases are present in more than 50 percent of patients with either NSCLC or SCLC [25,35]. (See "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer", section on 'Clinical-directed imaging'.)

Constitutional symptoms — Patients with lung cancer may also present with nonspecific symptoms that suggest the presence of advanced-stage disease. These symptoms include but are not limited to weight loss, anorexia, weakness, and fatigue. Reports of presenting symptoms of lung cancer show considerable variability in frequency of symptoms; for example, weight loss has been reported in 0 to 68 percent of patients and weakness in 0 to 10 percent [36]. One series of 3800 patients with lung cancer reported weight loss as a presenting symptom in only about 3 percent of patients, but patients experiencing it experienced a shortened survival relative to patients presenting with cough alone [6]. Fatigue is a less common symptom at presentation with lung cancer and becomes more common among patients undergoing treatment for lung cancer.

PARANEOPLASTIC PHENOMENA — Paraneoplastic effects of tumor are remote effects that are not related to the direct invasion, obstruction, or metastasis.

Hypercalcemia — Hypercalcemia in patients with lung cancer may arise from tumor secretion of parathyroid hormone-related protein, or less commonly from extensive bony metastases or primary hyperparathyroidism.

Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, lethargy, polyuria, polydipsia, and dehydration. Confusion and coma are late manifestations as are renal failure and nephrocalcinosis. (See "Clinical manifestations of hypercalcemia".)

Patients who are symptomatic from hypercalcemia, or have significantly elevated serum calcium levels, regardless of symptoms, require treatment that includes hydration and bisphosphonate [37]. The treatment of hypercalcemia due to malignancy is discussed in detail separately. (See "Hypercalcemia of malignancy: Mechanisms" and "Treatment of hypercalcemia".)

In one study of 1149 consecutive lung cancers, 6 percent had hypercalcemia [38]. Among those with hypercalcemia, squamous cell carcinoma, adenocarcinoma, and SCLC were responsible in 51, 22, and 15 percent of cases, respectively. Most patients with hypercalcemia have advanced disease (stage III or IV) and a limited survival [38]. (See "Hypercalcemia of malignancy: Mechanisms".)

SIADH secretion — The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is frequently caused by SCLC and results in hyponatremia. Approximately 10 percent of patients who have SCLC exhibit SIADH [39,40]. SCLC accounts for approximately 75 percent of all malignancy-related occurrences of SIADH. (See "Diagnostic evaluation of adults with hyponatremia" and "Pathophysiology and etiology of the syndrome of inappropriate antidiuretic hormone secretion (SIADH)".)

The severity of symptoms is related to the degree of hyponatremia and the rapidity of the fall in serum sodium. Symptoms include anorexia, nausea, and vomiting. Cerebral edema can occur when the onset of hyponatremia is rapid. Symptoms caused by cerebral edema may include irritability, restlessness, personality changes, confusion, coma, seizures, and respiratory arrest. (See "Manifestations of hyponatremia and hypernatremia in adults", section on 'Hyponatremia'.)

The treatment of SIADH focuses on treating the malignancy. In the majority of patients with SCLC, the hyponatremia will resolve within weeks of starting chemotherapy. Chronic hyponatremia or that of unclear duration may be treated with normal saline infusion to euvolemia, fluid restriction and demeclocycline, or a vasopressin-receptor antagonist. Acute and severe hyponatremia may be carefully treated with hypertonic (3 percent) saline infusion for a correction of 1 to 2 mmol per liter per hour with a correction of not more than 8 to 10 mmol per liter in 24 hours [41]. (See "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat".)

Neurologic syndromes — Lung cancer is the most common cancer associated with paraneoplastic neurologic syndromes; typically, these are associated with SCLC. Paraneoplastic neurologic syndromes are thought to be immune mediated, and autoantibodies have been identified in a number of instances. The various neurologic paraneoplastic syndromes and their pathophysiology are discussed elsewhere. (See "Paraneoplastic syndromes affecting spinal cord, peripheral nerve, and muscle" and "Overview of paraneoplastic syndromes of the nervous system" and "Paraneoplastic visual syndromes" and "Paraneoplastic cerebellar degeneration" and "Autoimmune (including paraneoplastic) encephalitis: Clinical features and diagnosis" and "Opsoclonus-myoclonus-ataxia syndrome".)

These diverse neurologic manifestations include, but are not limited to, Lambert-Eaton myasthenic syndrome (LEMS), cerebellar ataxia, sensory neuropathy, limbic encephalitis, encephalomyelitis, autonomic neuropathy, retinopathy, and opsomyoclonus [42].

The most common of these is LEMS, which may be seen in approximately 3 percent of patients with SCLC (waveform 1) [43]. The neurologic symptoms of LEMS precede the diagnosis of SCLC in more than 80 percent of cases, often by months to years. (See "Lambert-Eaton myasthenic syndrome: Clinical features and diagnosis" and "Lambert-Eaton myasthenic syndrome: Treatment and prognosis", section on 'Evaluation for malignancy'.)

As many as 70 percent of patients who have SCLC and an associated paraneoplastic neurologic syndrome have limited-stage disease [44]. The finding of a paraneoplastic autoantibody in patients presenting with a neurologic syndrome should lead to an evaluation for malignancy. A computed tomography (CT) of the chest is indicated in current or former smokers who have a suspected paraneoplastic neurologic syndrome. If the CT of the chest is negative, then positron emission tomography (PET) may be useful in identifying the location of a neoplasm. Even subtle abnormalities of the lungs or mediastinum require biopsy in this situation (image 10A-B) [45].

Paraneoplastic neurologic syndromes generally do not improve with immunosuppressive treatment. However, symptoms may stabilize with response of the underlying neoplasm to treatment. Exceptions include Lambert-Eaton myasthenic syndrome and opsoclonus-myoclonus syndrome; most patients may experience resolution or partial remission with immunosuppression and treatment of the cancer.

Hematologic manifestations — A number of hematologic abnormalities are seen in patients with lung cancer. These include the following:

●Anemia – Anemia is frequent in patients with lung cancer and can contribute to fatigue and dyspnea. As an example, in one series, 40 percent of untreated patients had a hemoglobin ≤12 g/dL, while the incidence of anemia was 80 percent in those on chemotherapy [46]. Anemia may be due to any of a number of causes, including microangiopathic hemolytic anemia and anemia of chronic disease. (See "Causes of anemia in patients with cancer" and "Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer".)

●Leukocytosis – In one series, tumor-associated leukocytosis was found in 15 percent of patients with lung cancer. Nearly all had NSCLC, and the leukocytosis was thought to be due to overproduction of granulocyte-colony stimulating factor [47]. Leukocytosis in association with lung cancer is associated with a poor prognosis and has also been associated with hypercalcemia [38,47]. (See "Approach to the patient with neutrophilia", section on 'Causes of neutrophilia'.)

●Thrombocytosis – Thrombocytosis is common and may be present in as many as 14 percent of patients with lung cancer at presentation [48]. Thrombocytosis at presentation has been identified as an independent predictor of shortened survival [49].

●Eosinophilia – Eosinophilia in tissue or blood is rare but has been reported in patients with large cell carcinoma. (See "Eosinophil biology and causes of eosinophilia".)

●Hypercoagulable disorders – A variety of hypercoagulable disorders have been associated with lung cancer and other malignancies. These hypercoagulable disorders include:

•Superficial thrombophlebitis (Trousseau syndrome)

•Deep venous thrombosis and thromboembolism

•Disseminated intravascular coagulopathy

•Thrombotic microangiopathy

•Nonbacterial thrombotic endocarditis

These complications and their management are discussed separately. (See "Risk and prevention of venous thromboembolism in adults with cancer" and "Diagnostic approach to suspected TTP, HUS, or other thrombotic microangiopathy (TMA)" and "Nonbacterial thrombotic endocarditis".)

Hypertrophic osteoarthropathy — Hypertrophic pulmonary osteoarthropathy (HPO) is defined by the presence of clubbing (picture 3) and periosteal proliferation of the tubular bones associated with lung cancer or other lung disease. Clinically, HPO is characterized by a symmetrical, painful arthropathy and long-bone pain that usually involves the ankles, knees, wrists, and elbows. The metacarpal, metatarsal, and phalangeal bones may also be involved. (See "Malignancy and rheumatic disorders", section on 'Hypertrophic osteoarthropathy'.)

A radiograph of the long bones (ie, femur, tibia, and fibula) shows characteristic periosteal new bone formation in patients with HPO. An isotope bone scan or PET typically demonstrates diffuse uptake by the long bones (image 11A-B). The symptoms of HPO may resolve after tumor resection. For patients who are not operable, the usual treatment is with nonsteroidal anti-inflammatory agents, corticosteroids, or a bisphosphonate [50].

Dermatomyositis and polymyositis — Dermatomyositis and polymyositis are two distinct forms of inflammatory myopathy, both of which are manifested clinically by muscle weakness. These inflammatory myopathies can be the presenting symptom in patients with lung cancer or can develop later in the course of disease. In addition to lung cancer, other frequent primary sites associated with these disorders include the ovary, cervix, pancreas, bladder, and stomach. The incidence of malignancy and the role of screening for cancer in patients with dermatomyositis or polymyositis are discussed elsewhere. (See "Malignancy in dermatomyositis and polymyositis".)

Cushing syndrome — Ectopic production of adrenal corticotropin can cause Cushing syndrome. Patients typically present with muscle weakness, weight gain, hypertension, hirsutism, and osteoporosis. However, when Cushing syndrome is due to SCLC, weight loss is more often present [51]. Hypokalemic alkalosis and hyperglycemia are usually present. (See "Epidemiology and clinical manifestations of Cushing syndrome".)

Cushing syndrome is rare, but is most commonly seen in patients with SCLC, large cell neuroendocrine carcinoma, or carcinoid tumors of the lung [52]. Patients with Cushing syndrome and SCLC appear to have a worse prognosis than patients with SCLC without Cushing syndrome [52-54]. (See "Establishing the cause of Cushing syndrome" and "Lung neuroendocrine (carcinoid) tumors: Epidemiology, risk factors, classification, histology, diagnosis, and staging", section on 'Cushing's syndrome'.)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Lung cancer (The Basics)" and "Patient education: Asbestos exposure (The Basics)")

●Beyond the Basics topics (see "Patient education: Lung cancer risks, symptoms, and diagnosis (Beyond the Basics)")

SUMMARY

●Introduction – Lung cancer is the most common cause of cancer mortality worldwide for both men and women. The majority of patients are symptomatic at presentation, although screening for lung cancer has been shown to save lives by detecting lung cancer in asymptomatic individuals at high risk. (See 'Introduction' above and "Screening for lung cancer".)

●Intrathoracic versus extrathoracic manifestations – The clinical manifestations of lung cancer can be due to intrathoracic effects of the tumor (eg, cough, hemoptysis, pleural disease), extrathoracic metastases (most commonly, liver, bone, brain), or paraneoplastic phenomena (eg, hypercalcemia, Cushing syndrome, hypercoagulability disorders, various neurologic syndromes). (See 'Intrathoracic clinical manifestations' above and 'Clinical manifestations of extrathoracic metastases' above.)

●Intrathoracic manifestations

•Cough – The new onset of cough in a smoker or former smoker should raise suspicion for lung cancer. Cough is present in 50 to 75 percent of lung cancer patients at presentation and occurs most frequently in patients with squamous cell and small cell carcinomas because of their tendency to involve central airways. (See 'Cough' above.)

•Shortness of breath – Shortness of breath is a common symptom in patients with lung cancer at the time of diagnosis, occurring in approximately 25 to 40 percent of cases. Dyspnea may be due to extrinsic or intraluminal airway obstruction, obstructive pneumonitis or atelectasis, lymphangitic tumor spread, tumor emboli, pneumothorax, pleural effusion, or pericardial effusion with tamponade. (See 'Chest pain' above.)

●Extrathoracic manifestations

•Bone – Metastasis from lung cancer to bone is frequently symptomatic. Pain in the back, chest, or extremity, and elevated levels of serum alkaline phosphatase are usually present in patients who have bone metastasis. The serum calcium may be elevated due to extensive bone disease. Approximately 20 percent of patients with non-small cell lung cancer have bone metastases on presentation. (See 'Bone' above.)

•Central nervous system – Symptoms from central nervous system metastasis are similar to those with other tumors and include headache, vomiting, visual field loss, hemiparesis, cranial nerve deficit, and seizures. (See 'Brain' above.)

•Hypercalcemia – Hypercalcemia in patients with lung cancer may arise from tumor secretion of parathyroid hormone-related protein or, less commonly, from extensive bony metastases. (See 'Hypercalcemia' above.)

•Syndrome of inappropriate antidiuretic hormone secretion (SIADH) – SIADH is frequently caused by small cell lung cancer (SCLC) and results in hyponatremia. Approximately 10 percent of patients who have SCLC exhibit SIADH. (See 'SIADH secretion' above.)