Lung Cancer Diagnosis Improved With Gene Test Plus Bronchoscopy

Emma Hitt, PhD

October 29, 2012

ATLANTA, Georgia — A combination of gene-expression testing (BronchoGen, Allegro Diagnostics) and diagnostic bronchoscopy significantly improves accuracy in the diagnosis of lung cancer, compared with bronchoscopy alone, according to the multicenter AEGIS (Airway Epithelium Gene Expression in the Diagnosis of Lung Cancer) clinical trial.

Duncan Whitney, PhD, from Allegro Diagnostics, in Maynard, Massachusetts, presented the study findings in a late-breaking oral session here at CHEST 2012: American College of Chest Physicians Annual Meeting.

"This test in combination with bronchoscopy has been shown to improve the sensitivity of cancer detection to 94%, reducing the number of false-negatives from 26% to 6%," Dr. Whitney told Medscape Medical News. It is expected that in clinical practice this will minimize surgery and other invasive procedures in benign cases, he noted.

In current clinical recommendations, bronchoscopy plays a central role in the diagnosis of lung cancer; however, diagnostic yields can vary, depending on the methods used to collect and process cells and the size and location of the lesion.

Dr. Whitney and colleagues sought to examine the use and assess the accuracy of gene-expression signature testing in patients undergoing bronchoscopy for suspected lung cancer.

They evaluated data from 330 patients who were enrolled in the AEGIS trial — a prospective, case-controlled, multicenter trial that collected bronchial epithelial cells from current and former smokers undergoing bronchoscopy for suspicion of lung cancer. In 240 patients with confirmed cancer and 90 control subjects, main-stem bronchial airway brushings were collected and analyzed, microarray analysis was performed, and a gene-expression prediction model was optimized.

The polymerase chain reaction gene-expression test evaluating 30 genes yielded a sensitivity of 77% (95% confidence interval [CI], 71% to 83%). The combination of bronchoscopy plus the gene-expression test yielded a sensitivity of 94% (95% CI, 91% to 97%); for bronchoscopy alone, the sensitivity was 74% (95% CI, 68% to 80%).

The test also improved negative-predictive value. For the genetic test plus bronchoscopy, the negative-predictive value was 0.85 (95% CI, 0.80 to 0.90); for bronchoscopy alone, it was 0.65 (95% CI, 0.59 to 0.71).

"This study confirms the accuracy of gene-expression testing in combination with diagnostic bronchoscopy for suspected lung cancer," the researchers conclude.

"In current practice, even with the best bronchoscopic techniques in the top pulmonology centers, approximately 30% of procedures are inconclusive or nondiagnostic, on average," Dr. Whitney said. "This leads to a negative-predictive value in the range of 60%," he said.

"Currently, pulmonologists often refer nondiagnostic cases to more invasive follow-up procedures, such as transthoracic needle aspirations or surgery (namely, thoracotomy), to avoid missing cancers," he said. "These invasive procedures carry elevated associated risk, morbidity, and cost," he added.

Independent commentator Guy Adami, PhD, from the University of Illinois at Chicago, described a study by Spira and colleagues that evaluated an 80-gene classifier that used RNA from bronchial brushings to identify patients with lung cancer (Cancer Prev Res [Phila]. 2008;1:396-403). "This showed 84% sensitivity and 84% specificity, and slighter poorer results with patients from independent clinics," he told Medscape Medical News.

In the AEGIS study, a "reoptimized" classifier predicts the presence of lung cancer on the basis of the level of expression of 30 genes, Dr. Adami explained. He added that this gene-expression test has a higher sensitivity than cytopathology, which is currently used to diagnose lung cancer.

According to Dr. Adami, it is "remarkable that sampling the main-stem bronchial airway provides an indication of the presence of cancer deeper in the lung." It is also remarkable because a surgical biopsy is not needed; taking cells with a cytological brush for RNA analysis is a much less invasive approach, he said.

"Given the low sensitivity of cytopathology testing for lung cancer, this new gene-expression-based test has value, especially since it can be done with cells taken during the same bronchoscopy, so it does not add a new procedure," he said. "The specificity of the cytopathology test is 100%, so it makes sense to use both tests.... They seem to complement each other," Dr. Adami noted.

This study was funded by Allegro Diagnostics. All of the study authors report financial relationships with Allegro Diagnostics. Dr. Adami has disclosed no relevant financial relationships.

CHEST 2012: American College of Chest Physicians Annual Meeting. Presented October 23, 2012