In 2003, the American College of Chest Physicians (ACCP) Health and Science Policy Committee published a guideline for the diagnosis and management of lung cancer to address the growing prevalence of the disease. Although research has advanced significantly since the publication of this guideline, incidence and mortality rates continue to increase. Lung cancer is the most common cause of cancer deaths in the United States, and more than 200,000 newly diagnosed cases were expected in 2007. The ACCP has revised the original guideline to update evidence supporting the original recommendations and to include additional relevant topics.

Chemoprophylaxis

Smoking is the main risk factor for lung cancer; current smokers have a 10-fold higher risk than persons who have never smoked. Although smoking prevention and cessation programs are essential to decrease the incidence of lung cancer, former smokers have a substantially higher risk of lung cancer than persons who never smoked; and more than one half of lung cancer cases occur in former smokers. Recent efforts to decrease this number have focused on chemoprophylaxis to reduce carcinogenesis in at-risk patients.

The goal of chemoprophylaxis is to reverse, suppress, or prevent the process of carcinogenesis using an effective agent that has a favorable toxicity profile. Agents that have been studied include retinoids, folate and vitamin B₁₂, and budesonide. Trials of selenium and cyclooxygenase-2 inhibitors are underway. Although new research on chemoprophylaxis for lung cancer is emerging, sufficient data are not available to recommend the use of any agent alone or in combination for primary, secondary, or tertiary lung cancer chemoprophylaxis outside a clinical trial in persons who are at risk of lung cancer or who have a history of lung cancer.

Screening

Although early-stage lung cancer is treatable, most patients do not present with symptoms until the disease is in the advanced stages. A screening test that detects lung cancer before it spreads may reduce mortality rates. Studies have examined the use of chest radiography, sputum cytology, and low-dose computed tomography (CT) for screening asymptomatic patients with no history of cancer.

CHEST RADIOGRAPHY AND SPUTUM CYTOLOGY

In asymptomatic patients with no history of lung cancer, serial chest radiography and sputum cytology (single or serial) are not recommended to screen for lung cancer. Studies of chest radiography have shown that the technique increases detection of early-stage lung cancer; however, it does not reduce the incidence of late-stage cancer or related mortality. This may be because screening misses rapidly progressing cancers and detects less aggressive lung cancers that are unlikely to progress to clinical disease.

Supplementing radiography findings with sputum cytology findings has not been shown to provide increased mortality benefit. Studies of other biomarker tests (e.g., screening the breath for volatile organic compounds and DNA alterations, proteomic profiling of tissue) have shown promise, although more research is needed.

LOW-DOSE CT

Although low-dose CT is the most promising screening technique for lung cancer, it is not recommended outside well-designed clinical trials in asymptomatic patients with no history of lung cancer. Studies have shown that CT detects approximately three times as many small nodules as does chest radiography; however, these results are from uncontrolled, observational studies. This makes it difficult to determine whether it detects more aggressive cancer than chest radiography or whether it detects more nonaggressive nodules, leading to an increase in unnecessary medical procedures.

Randomized controlled trials of low-dose CT are ongoing. The results of these trials will help determine whether low-dose CT reduces mortality rates, is cost-effective, or leads to overdiagnosis.

Diagnosis of Pulmonary Nodules

Pulmonary nodules are common findings in clinical practice and can be difficult to manage, especially if the nodule is very small. “Subcentimeter” nodules called solitary pulmonary nodules (SPNs) are becoming more prevalent. SPNs appear on radiographs as a single spherical, well-circumscribed opacity measuring 3 cm or less in diameter. Evaluation of patients with pulmonary nodules should be based on the probability of malignancy and imaging test results.

PROBABILITY OF MALIGNANCY

In every patient with an SPN, physicians should estimate the pretest probability of malignancy using clinical judgement or a validated prediction model. Most lung nodules are detected on unrelated radiographs or CT scans. The prevalence of malignancy varies, but an estimated pretest probability of malignancy will help guide diagnostic testing, such as imaging studies or biopsy. Although most physicians use clinical judgement to predict the risk of malignancy, there are several models to help with the estimation.

IMAGING TESTS

Initial diagnosis of pulmonary nodules includes imaging studies. Chest radiography and CT are useful and widely available. Recently, contrast-enhanced CT and fluorodeoxyglucose positron emission tomography (PET) have gained attention for use in the diagnosis of pulmonary nodules. Magnetic resonance imaging has a limited role, if any, in most patients.

Chest Radiography. Diagnosis of an SPN begins with a review of chest radiographs. Nodules should be examined in multiple views. Because nodules that have been stable for at least two years do not require further diagnostic evaluation, current and previous chest radiographs should be compared in all patients with an SPN to determine the growth rate. If there is clear evidence of growth, tissue diagnosis is recommended.

A presumptive benign diagnosis can be made if there are characteristic patterns of calcification. However, other patterns of calcification (e.g., stippled and eccentric patterns) do not rule out malignancy, and further evaluation is needed.

Chest CT. Chest CT has a higher sensitivity and specificity for detecting nodules compared with chest radiography. Thus, CT provides more specific information about the location, density, and edge characteristics of nodules detected on chest radiography and may identify unsuspected lymphadenopathy, synchronous parenchymal lesions, or invasion of the chest wall or mediastinum.

All patients with an indeterminate SPN visible on chest radiography should receive chest CT, preferably with thin sections through the nodule. The likelihood of nodule detection using CT increases as slice thickness decreases. As with chest radiography, previous CT scans should be reviewed if an SPN is visible on a current chest CT. Morphologic characteristics on chest CT can suggest malignancy or lead to a presumptive benign diagnosis.

Chest CT with dynamic contrast media has been shown to be highly sensitive, but nonspecific for detecting malignant nodules. Therefore, it may be an option in patients with normal renal function and an indeterminate SPN finding on chest radiography or CT.

Fluorodeoxyglucose PET. Fluorodeoxyglucose PET is a noninvasive imaging technique widely used for tumor diagnosis and staging. Preliminary evidence suggests that f luorodeoxyglucose PET can help characterize nodules that are at least 8 to 10 mm in diameter; however, false-negative results and occasional false-positive results may occur. The use of fluorodeoxyglucose PET may be most cost-effective in patients with a pretest probability for malignancy that is discordant with CT findings, especially when the pretest probability is relatively low and CT findings are indeterminate.

Fluorodeoxyglucose PET is recommended to characterize the SPN in patients with a low-to-moderate pretest probability of malignancy and an indeterminate nodule measuring at least 8 to 10 mm in diameter, and in patients with a high pretest probability or a sub-centimeter nodule measuring less than 8 to 10 mm in diameter.

Initial Diagnosis of Suspected Lung Cancer

Several techniques are used to confirm the diagnosis of suspected lung cancer, including sputum cytology, flexible bronchoscopy, and transthoracic needle aspiration. Diagnoses should be obtained using the easiest method in patients with presumed small cell lung cancer or with clear evidence of advanced non–small cell lung cancer; size and location of the primary tumor, metastasis, and overall clinical status of the patient can aid further diagnostic testing decisions.

SPUTUM CYTOLOGY

Although sputum cytology is the least invasive diagnostic test, its accuracy is dependent on the technique used (e.g., number of samples, specimen adequacy). If lung cancer is suspected, sputum cytology is acceptable for patients presenting with a central lesion with or without radiographic evidence of metastasis in whom more invasive procedures pose a higher risk. Further testing should be performed if sputum cytology findings are nondiagnostic and the suspicion of lung cancer remains.

FLEXIBLE BRONCHOSCOPY

The decision to use flexible bronchoscopy is largely based on tumor location (central or peripheral). Central lesions can appear as exophytic endobronchial masses, submucosal spread, or a peribronchial tumor causing extrinsic compression. Peripheral lesions cannot be seen beyond the visual segmental bronchi.

Central Lesions. Data show that flexible bronchoscopy has an overall sensitivity of about 0.88 in the diagnosis of central lesions. Direct forceps biopsy (at least three are recommended) is the most common technique. Although the use of washing and brushing is less effective, the technique is often combined with direct forceps biopsy. Adding transbronchial needle aspiration increases the sensitivity of bronchoscopy in patients with submucosal tumor spread or a peribronchial tumor causing extrinsic compression. Bronchoscopy is recommended to confirm the diagnosis in patients with a central lesion; however, further testing should be performed if bronchoscopy results are nondiagnostic and the suspicion of lung cancer remains.

Peripheral Lesions. Bronchoscopy is less sensitive for diagnosing peripheral lesions than for central lesions. Transbronchial biopsies have the highest sensitivity, followed by brush biopsy and bronchoalveolar lavage or washings. Sensitivity of bronchoscopy for peripheral lesions is most affected by the size of the lesion.

Ultrasound Probes. Studies have evaluated whether endobronchial ultrasound probes (radial and convex) aid in the bronchoscopic diagnosis of lung cancer. Radial probes are used in the diagnosis of peripheral lesions. Data show that radial probes can significantly increase the diagnostic yield of flexible bronchoscopy when evaluating peripheral lesions less than 20 mm in diameter. Therefore, the technique can be considered before referring these patients for transthoracic needle aspiration. Because only preliminary data are available, no recommendation can be made about the use of convex probes.

TRANSTHORACIC NEEDLE ASPIRATION

Transthoracic needle aspiration is more sensitive than bronchoscopy for the diagnosis of peripheral lung lesions; CT-guided studies are more sensitive than fluoroscopy-guided studies. If tissue diagnosis is needed before further management can be determined, transthoracic needle aspiration is recommended in patients with a small (less than 2 cm) peripheral lesion. Further testing should be performed if transthoracic needle aspiration results are nondiagnostic and the suspicion of lung cancer remains.