Chest
Volume 143, Issue 5, Supplement, May 2013, Pages e142S-e165S
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Establishing the Diagnosis of Lung Cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines

https://doi.org/10.1378/chest.12-2353Get rights and content

Background

Lung cancer is usually suspected in individuals who have an abnormal chest radiograph or have symptoms caused by either local or systemic effects of the tumor. The method of diagnosis of lung cancer depends on the type of lung cancer (small cell lung cancer or non-small cell lung cancer [NSCLC]), the size and location of the primary tumor, the presence of metastasis, and the overall clinical status of the patient. The objective of this study was to determine the test performance characteristics of various modalities for the diagnosis of suspected lung cancer.

Methods

To update previous recommendations on techniques available for the initial diagnosis of lung cancer, a systematic search of the MEDLINE, Healthstar, and Cochrane Library databases covering material to July 2011 and print bibliographies was performed to identify studies comparing the results of sputum cytology, conventional bronchoscopy, flexible bronchoscopy (FB), electromagnetic navigation (EMN) bronchoscopy, radial endobronchial ultrasound (R-EBUS)-guided lung biopsy, transthoracic needle aspiration (TTNA) or biopsy, pleural fluid cytology, and pleural biopsy with histologic reference standard diagnoses among at least 50 patients with suspected lung cancer. Recommendations were developed by the writing committee, graded by a standardized method (see the article “Methodology for Development of Guidelines for Lung Cancer” in this guideline), and reviewed by all members of the Lung Cancer Guideline Panel prior to approval by the Thoracic Oncology NetWork, the Guidelines Oversight Committee, and the Board of Regents of the American College of Chest Physicians.

Results

Sputum cytology is an acceptable method of establishing the diagnosis of lung cancer, with a pooled sensitivity rate of 66% and a specificity rate of 99%. However, the sensitivity of sputum cytology varies according to the location of the lung cancer. For central, endobronchial lesions, the overall sensitivity of FB for diagnosing lung cancer is 88%. The diagnostic yield of bronchoscopy decreases for peripheral lesions. Peripheral lesions < 2 or > 2 cm in diameter showed a sensitivity of 34% and 63%, respectively. R-EBUS and EMN are emerging technologies for the diagnosis of peripheral lung cancer, with diagnostic yields of 73% and 71%, respectively. The pooled sensitivity of TTNA for the diagnosis of lung cancer was 90%. A trend toward lower sensitivity was noted for lesions < 2 cm in diameter. TTNA is associated with a higher rate of pneumothorax compared with bronchoscopic procedures. In a patient with a malignant pleural effusion, pleural fluid cytology is reported to have a mean sensitivity of about 72%. A definitive diagnosis of metastatic disease to the pleural space can be estalished with a pleural biopsy. The diagnostic yield for closed pleural biopsy ranges from 38% to 47% and from 75% to 88% for image-guided closed biopsy. Thoracoscopic biopsy of the pleura carries the highest diagnostic yield, 95% to 97%. The accuracy in differentiating between small cell and non-small cell cytology for the various diagnostic modalities was 98%, with individual studies ranging from 94% to 100%. The average false-positive and false-negative rates were 9% and 2%, respectively. Although the distinction between small cell and NSCLC by cytology appears to be accurate, NSCLCs are clinically, pathologically, and molecularly heterogeneous tumors. In the past decade, clinical trials have shown us that NSCLCs respond to different therapeutic agents based on histologic phenotypes and molecular characteristics. The physician performing diagnostic procedures on a patient suspected of having lung cancer must ensure that adequate tissue is acquired to perform accurate histologic and molecular characterization of NSCLCs.

Conclusions

The sensitivity of bronchoscopy is high for endobronchial disease and poor for peripheral lesions < 2 cm in diameter. The sensitivity of TTNA is excellent for malignant disease, but TTNA has a higher rate of pneumothorax than do bronchoscopic modalities. R-EBUS and EMN bronchoscopy show potential for increasing the diagnostic yield of FB for peripheral lung cancers. Thoracoscopic biopsy of the pleura has the highest diagnostic yield for diagnosis of metastatic pleural effusion in a patient with lung cancer. Adequate tissue acquisition for histologic and molecular characterization of NSCLCs is paramount.

Section snippets

General Approach to Diagnosis

2.3.1. In patients suspected of having small cell lung cancer (SCLC) based on the radiographic and clinical findings, it is recommended that the diagnosis be confirmed by the least invasive method (sputum cytology, thoracentesis, fine needle aspiration [FNA], bronchoscopy including transbronchial needle aspiration [TBNA]), as dictated by the patient's presentation (Grade 1C).

2.3.2. In patients suspected of having lung cancer, who have extensive infiltration of the mediastinum based on

Methods

This article updates previous ACCP Lung Cancer Guidelines.19, 20 The data from these previous editions were included and updated as described later. Where new technology or procedures became available, new data summaries were developed. In addition, because of the increasing importance of distinguishing the cell type of NSCLC in the identification of genetic mutations, a discussion of how this impacts diagnostic procedures has been included.

In collaboration with an ACCP methodologist, the

Thoracentesis

Patients with suspected lung cancer who present with a pleural effusion should undergo thoracentesis. Cytologic examination of the pleural fluid is a quick and minimally invasive way to differentiate between a malignant effusion (due to malignant involvement of the pleura) and a paramalignant effusion (due to other factors such as lymphatic blockade, atelectasis, or hypoproteinemia). Distinction between the two has particular clinical relevance because the finding of malignant cells in the

Diagnosis of Primary Tumor

A variety of techniques (sputum cytology, FB, EMN bronchoscopy, R-EBUS, TTNA) are available as methods to establish a definitive diagnosis. The main goals in selecting a specific diagnostic modality are (1) to maximize the yield of the selected procedure for both diagnosis and staging and (2) to avoid unnecessary invasive tests for the patient, with special attention to the projected treatment plan. For the first edition of the ACCP Lung Cancer Guidelines, key questions were formulated to

Conclusion

A variety of techniques are available to assist the physician in achieving a definitive diagnosis of lung cancer. Selection of the most appropriate test is best done in a multidisciplinary fashion with input from a pulmonologist, a chest radiologist, a thoracic surgeon, and a pathologist. Furthermore, the most appropriate test is usually determined by the type of lung cancer (SCLC or NSCLC), the size and location of the tumor, and the presumed stage of the cancer.

A diagnosis should be obtained

Acknowledgments

Author contributions: Dr Rivera had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Dr Rivera: contributed to the writing of all sections and recommendations except for the navigation bronchoscopy and R-EBUS sections and recommendations; the evidence review for PICO questions 2, 3, 6, and 7 to update these sections; and the review and editing of the manuscript.

Dr Mehta: contributed to the writing of the

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    Funding/Sponsors: The overall process for the development of these guidelines, including matters pertaining to funding and conflicts of interest, are described in the methodology article.1 The development of this guideline was supported primarily by the American College of Chest Physicians. The lung cancer guidelines conference was supported in part by a grant from the Lung Cancer Research Foundation. The publication and dissemination of the guidelines was supported in part by a 2009 independent educational grant from Boehringer Ingelheim Pharmaceuticals, Inc.

    COI Grids reflecting the conflicts of interest that were current as of the date of the conference and voting are posted in the online supplementary materials.

    Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://dx.doi.org/10.1378/chest.1435S1.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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