Bronchial Gene-Expression Classifier Improves Bronchoscopy Performance in Diagnosing Lung Cancer
In a study reported in The New England Journal of Medicine, Silvestri et al of the AEGIS study team found that use of a bronchial airway gene-expression classifier improved the diagnostic performance of bronchoscopy in patients being evaluated for suspected lung cancer.
Study Details
The study involved current or former smokers undergoing bronchoscopy for suspected lung cancer in the prospective AEGIS-1 (N = 298) and AEGIS-2 (N = 341) studies. A gene-expression classifier was measured in epithelial cells from normal-appearing mainstem bronchus to assess the probability of lung cancer.
Bronchoscopy Findings
Among the total of 639 patients, 43% of bronchoscopic examinations were nondiagnostic for lung cancer, including in 120 (25%) of 487 patients with an ultimate diagnosis of lung cancer. The sensitivity of bronchoscopy for the detection of lung cancer was 74% in AEGIS-1 and 76% in AEGIS-2. In 267 evaluable patients with nondiagnostic bronchoscopic examination, 170 (64%) underwent an invasive procedure, including 52 (35%) of 147 with benign lesions. Of 76 patients undergoing surgical lung biopsy, 27 (36%) had benign lesions.
Use of Classifier
In AEGIS-1, the genomic classifier had an area under the receiver-operating-characteristic curve (AUC) of 0.78, sensitivity of 88%, and specificity of 47%. In AEGIS-2, the classifier had an AUC of 0.74, sensitivity of 89%, and specificity of 47%. The combination of the classifier plus bronchoscopy had a sensitivity of 96% in AEGIS-1 and 98% in AEGIS-2. In the total population, sensitivity with the classifier and bronchoscopy was 96% to 97% for lesion sizes of < 2 to > 3 cm and 95% to 99% for central, peripheral, and central and peripheral lesions. Sensitivity of bronchoscopy plus the classifier was 100%, 93%, 98%, and 97% in patients with a low, intermediate, high, and unknown pretest probability of cancer.
In 101 patients with an intermediate pretest probability of cancer, the negative predictive value of the classifier was 91% among patients with a nondiagnostic bronchoscopic examination.
The investigators concluded: “The gene-expression classifier improved the diagnostic performance of bronchoscopy for the detection of lung cancer. In intermediate-risk patients with a nondiagnostic bronchoscopic examination, a negative classifier score provides support for a more conservative diagnostic approach.”
Avrum Spira, MD, of Boston University Medical Center, is the corresponding author of The New England Journal of Medicine article. Gerard A. Silvestri, MD, of Medical University of South Carolina, and Anil Vachani, MD, of University of Pennsylvania School of Medicine, contributed equally to the article.
The study was funded by Allegro Diagnostics and others. For full disclosures of the study authors, visit www.nejm.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
