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Am Fam Physician. 2022;105(5):487-494

Patient information: See related handout on lung cancer, written by the authors of this article.

Published online April 1, 2022.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial relationships.

Lung cancer is the second most common cancer in men and women in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. The most common but nonspecific symptom of lung cancer is cough. Associated symptoms, including hemoptysis or shortness of breath, or systemic symptoms, including anorexia or weight loss, greatly increase the likelihood of having lung cancer. Referral to a multidisciplinary lung cancer team, imaging, and confirmation through sputum cytology, thoracentesis, fine-needle aspiration, or mediastinoscopy are recommended. If lung cancer is confirmed, treatment options vary based on staging, histology, immunotherapy biomarker testing, and patient health status. Treatments include surgical resection, immunotherapy, chemotherapy, and/or radiotherapy. Family physicians should focus on primary prevention of lung cancer by encouraging tobacco cessation and early recognition by screening at-risk individuals and following guidelines for pulmonary nodules. As of 2021, the U.S. Preventive Services Task Force recommends annual lung cancer screening using low-dose computed tomography starting at 50 years of age in patients with a 20 pack-year history.

Lung cancer remains the leading cause of cancer-related death in the United States and worldwide; in the United States, it is the second most common cancer among men and women.1,2 The majority of lung cancers are divided into two histologic types: non–small cell lung cancer (NSCLC; 84%) and small cell lung cancer (SCLC; 13%), which helps guide treatment.3 Smoking is closely linked to 80% to 90% of lung cancer deaths, whereas radon exposure is a leading cause of nonsmoking-related lung cancer.4 Several guidelines address the management of lung cancer, with the goal of improving patient outcomes.5 In the United Kingdom, the National Institute for Health and Care Excellence has developed clinical pathways that were last updated in 2019, whereas in the United States, the most recent comprehensive lung cancer guideline from the American College of Chest Physicians was last updated in 2013, with more recent treatment recommendations from the National Comprehensive Cancer Network.2,68

Clinical recommendation Evidence rating Comments
The initial evaluation for lung cancer begins with laboratory testing, including a complete blood count, serum chemistries, calcium levels, liver function tests, and chest radiography; CT of the chest with intravenous contrast media should be performed when there is a high level of suspicion, even if radiographic results are normal.2,9,10,1315 C Practice guidelines, expert opinion, disease-oriented studies
Adults 50 to 80 years of age who have a 20 pack-year smoking history and currently smoke or have quit smoking within the past 15 years should undergo annual low-dose CT screening.36,40,44 B USPSTF and AAFP guidelines and limited evidence from one large, randomized controlled trial showing moderate benefit
Patients with lung cancer should be offered smoking cessation interventions.45 B Cochrane review that shows reduction in morbidity and mortality; no randomized controlled trials to identify specific smoking cessation interventions are recommended
Patients with lung cancer can improve symptoms with exercise training and nurse counseling.46,47 B Cochrane reviews, with studies limited by heterogeneity, small sample sizes, and high risk of bias
RecommendationSponsoring organization
Do not perform CT screening for lung cancer among patients at low risk of lung cancer.American College of Chest Physicians/American Thoracic Society
Do not recommend screening for breast, colorectal, prostate, or lung cancers without considering life expectancy and the risks of testing, overdiagnosis, and overtreatment.American Geriatrics Society
Do not perform CT surveillance for evaluation of indeterminate pulmonary nodules at more frequent intervals or for a longer period of time than recommended by established guidelines.American College of Chest Physicians/American Thoracic Society

Clinical Presentation and Diagnosis

IN-OFFICE EVALUATION

When evaluating a patient for lung cancer, a detailed history and physical examination should be performed, including environmental and work exposures. Current smoking or history of smoking is the single most important risk factor for all types of lung cancer.9,10 Concomitant chronic lung disease or exposure to radon or asbestos may increase the risk of lung cancer.10

Patients with lung cancer typically present with symptoms,11 the most common of which is cough.9,11 Hemoptysis in combination with weight loss, loss of appetite, or shortness of breath increases the likelihood of lung cancer.11 Table 1 provides signs and symptoms of lung cancer due to local effects,12 and Table 2 and Table 3 show, respectively, advanced disease–displaying symptoms of distant metastases and paraneoplastic syndromes associated with lung cancer.12

Sign/symptom of the primary tumor*LR+LR–
Digital clubbing55.00.96
Hemoptysis13.20.81
Weight loss6.20.76
Loss of appetite4.80.84
Dyspnea3.60.52
Chest or rib pain3.30.68
Fatigue2.30.76
First visit for cough2.20.50
Second visit for cough3.20.66
Third visit for cough4.20.77
Sign/symptom of intrathoracic spreadClinical context

Decreased breath sounds and dyspneaMalignant pleural effusion
Decreased heart sounds and enlarged cardiac silhouetteMalignant pericardial effusion
DysphagiaEsophageal invasion
Elevated hemidiaphragmPhrenic nerve paralysis
Facial swelling, plethora, and upper extremity edemaSuperior vena cava syndrome
Hoarseness, weak coughRecurrent laryngeal nerve palsy
Pleuritic chest painChest wall invasion
Ptosis, miosis, facial anhidrosisHorner syndrome (sympathetic chain compression)
Shoulder pain and muscle wasting along C8-T3 nerve rootPancoast tumor (superior sulcus tumor)
SiteSign or symptomFrequency (%)
AnyAny sign or symptom33
LiverWeakness, weight loss, anorexia, hepatomegalyUp to 60
BonePain, fracture, elevated alkaline phosphataseUp to 25
LymphaticsLymphadenopathy15 to 20
BrainHeadaches, seizures, nausea and vomiting, mental status changesUp to 10
AdrenalsAdrenal insufficiencyRare
SkinSubcutaneous nodulesRare
SyndromeFrequency (%)Comments
Systemic (anorexia, cachexia, weight loss, fatigue, fever)0 to 68May be readily apparent and striking
Digital clubbing29More common with non–small cell lung cancer
Hypercalcemia10 to 20Ectopic production of parathyroid hormone–related peptide; may be life-threatening
Hyponatremia1 to 5Syndrome of inappropriate antidiuretic hormone or ectopic production of atrial natriuretic peptide
Paraneoplastic encephalitis0.2Mental status changes
Cushing syndromeRareEctopic production of adrenocorticotropic hormone
Hypertrophic osteoarthropathyRareTriad of clubbing, arthralgias, and ossifying periostitis
Muscular weaknessRareLambert-Eaton myasthenic syndrome

The initial evaluation for patients with a suspicion for lung cancer begins with laboratory testing, including a complete blood count, serum chemistries, calcium levels, and liver function tests, with chest radiography.2,9 A normal chest radiograph alone should not be used to rule out lung cancer because just under 20% to 25% of normal chest radiographs may miss the disease.13,14 Patients who have a high level of suspicion for lung cancer based on clinical assessment or initial chest radiography findings should receive computed tomography (CT) of the chest with intravenous contrast media, ideally to include the liver and adrenals.2,15

PULMONARY NODULE FOLLOW-UP

Among patients presenting with incidental nodules found on radiographic imaging, follow-up for those older than 35 years is assessed based on features and risk categorization, as recommended by the Fleischner Society, updated in 2017 (Table 4).16,17 New studies are emerging on the use of genomic classifiers and artificial intelligence to help facilitate clinical management of incidental nodules.18,19 For patients meeting high-risk criteria and undergoing lung cancer screening, appropriate follow-up recommendations should be determined by the 2019 Lung-RADS guidelines20 (eTable A).

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