Chest
Volume 132, Issue 3, Supplement, September 2007, Pages 94S-107S
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DIAGNOSIS AND MANAGEMENT OF LUNG CANCER: ACCP GUIDELINES (2ND EDITION)
Evidence for the Treatment of Patients With Pulmonary Nodules: When Is It Lung Cancer?: ACCP Evidence-Based Clinical Practice Guidelines (2nd Edition)

https://doi.org/10.1378/chest.07-1352Get rights and content

Background

The solitary pulmonary nodule (SPN) is a frequent incidental finding that may represent primary lung cancer or other malignant or benign lesions. The optimal management of the SPN remains unclear.

Methods

We conducted a systematic literature review to address the following questions: (1) the prevalence of SPN; (2) the prevalence of malignancy in nodules with varying characteristics (size, morphology, and type of opacity); (3) the relationships between growth rates, histology, and other nodule characteristics; and (4) the performance characteristics and complication rates of tests for SPN diagnosis. We searched MEDLINE and other databases and used previous systematic reviews and recent primary studies.

Results

Eight large trials of lung cancer screening showed that both the prevalence of at least one nodule (8 to 51%) and the prevalence of malignancy in patients with nodules (1.1 to 12%) varied considerably across studies. The prevalence of malignancy varied by size (0 to 1% for nodules < 5 mm, 6 to 28% for nodules 5 to 10 mm, and 64 to 82% for nodules > 20 mm). Data from six studies of patients with incidental or screening-detected nodules showed that the risk for malignancy was approximately 20 to 30% in nodules with smooth edges; in nodules with irregular, lobulated, or spiculated borders, the rate of malignancy was higher but varied across studies from 33 to 100%. Nodules that were pure ground-glass opacities were more likely to be malignant (59 to 73%) than solid nodules (7 to 9%). The sensitivity of positron emission tomography imaging for identifying a malignant SPN was consistently high (80 to 100%), whereas specificity was lower and more variable across studies (40 to 100%). Dynamic CT with nodule enhancement yielded the most promising sensitivity (sensitivity, 98 to 100%; specificity, 54 to 93%) among imaging tests. In studies of CT-guided needle biopsy, nondiagnostic results were seen approximately 20% of the time, but sensitivity and specificity were excellent when biopsy yielded a specific benign or malignant result.

Conclusions

The prevalence of an SPN and the prevalence of malignancy in patients with an SPN vary widely across studies. The interpretation of these variable prevalence rates should take into consideration not only the nodule characteristics but also the population at risk. Modern imaging tests and CT-guided needle biopsy are highly sensitive for identifying a malignant SPN, but the specificity of imaging tests is variable and often poor.

Section snippets

Materials and Methods

The review methods were defined prospectively in a written protocol. The SPN Guideline Subcommittee, who authored the accompanying guideline, was consulted. Primary outcomes included prevalence of SPNs, stratified by smoking status, age, and other risk factors; prevalence of malignancy associated with specific nodule characteristics; histologic type and growth rates associated with specific nodule characteristics; diagnostic accuracy (sensitivity, specificity) of tests to determine whether a

What Is the Prevalence of SPNs?

From the literature review, eight large studies4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18 of lung cancer screening were identified (Table 1). It is important to note that nodules that are detected in screening studies differ in important ways from nodules that are detected in routine clinical practice. In screening studies, the nodules tend to be smaller, the prevalence of malignant nodules is much lower, and the tumor volume doubling times (VDTs) of malignant nodules are generally

What Is the Prevalence of Malignancy in Nodules With Varying Characteristics?

We identified three nodule characteristics for analysis: size, morphology, and type of opacity (Table 234). Seven studies5, 9, 16, 19, 20, 21, 22 that assessed nodule size found a proportional increase in the risk for malignancy as the diameter of the nodule increased (Table 2). With the exception of one small retrospective study20 in which two of two nodules < 5 mm in diameter were malignant, the prevalence of malignancy in nodules that measured < 5 mm was exceedingly low (range, 0 to 1%). The

What Is the Histologic Type and Natural History (Growth Rate) of Small Pulmonary Nodules With Varying Characteristics?

Nine studies9, 10, 27, 28, 29, 30, 31, 32, 33 analyzed the histology of pulmonary nodules with purely or primarily ground-glass attenuation on HRCT (Table 5). Bronchioloalveolar carcinoma (BAC) was the most common histologic subtype in such nodules (range, 70 to 100%).

Hasegawa et al10 reported the VDT for malignant SPNs on the basis of their morphologic characteristics: 813 ± 375 days for pure ground-glass opacities, 457 ± 260 days for mixed or partial ground-glass opacities, and 149 ± 125 days

What Are the Performance Characteristics of Tests for SPN Diagnosis?

An abundant body of evidence exists for the performance of positron emission tomography (PET) in the evaluation of SPN. Except for one study, the sensitivity of PET for identifying malignancy was consistently high (80 to 100%; Table 6).34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 In contrast, the specificity of PET was lower and highly variable (40 to 100%). The point on the summary receiver operating characteristic curve that corresponded to the median specificity

What Is the Prevalence of SPNs?

The prevalence of SPNs (8 to 51%) and the prevalence of malignancy in patients with SPNs (1.1 to 12%) varied significantly across studies. This variation stems from the inconsistency among studies in method, enrolled population, and reporting of results.

What Is the Prevalence of Malignancy in Nodules With Varying Characteristics (Size, Morphology, and Type of Opacity)?

The prevalence of malignancy in SPNs increased in proportion to size: 0 to 1% for nodules < 5 mm, 6 to 28% for nodules 5 to 10 mm, and 64 to 82% for nodules > 20 mm. Data from six studies9, 21, 22, 23, 24, 25 of patients with incidental or

Discussion

In patients with incidentally detected SPNs, treatment goals include prompt identification of malignant nodules to permit timely surgical resection and avoidance of surgery (when possible) in patients with benign nodules. Patients with SPNs and their clinicians confront challenging treatment decisions and must weigh the risks and benefits of various treatment strategies. Our report sought answers to key questions that are frequently posed when an SPN is encountered.

Our first question addressed

Conclusions

Our report sought evidence related to the prevalence of SPNs, the prevalence of malignancy in patients with SPNs, characteristics of SPNs associated with malignancy, and accuracy of tests that are used for SPN diagnosis. It is clear that further research is needed to address vital questions such as the prevalence of SPNs in the population at large, the characteristics that indicate malignancy, and the best management strategy. Essential steps toward more rigorous research must include the

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    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

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