Detecting Colorectal Adenomas and Cancer Using Volatile Organic Compounds in Exhaled Breath: A Proof-of-Principle Study to Improve Screening

BACKGROUND: Early detection of colorectal cancer (CRC) via screening programs is crucial as survival rates worsen at advanced stages. However, the currently used screening method such as the fecal immunochemical test (FIT) suffers from a high number of false positives and is insensitive for detecting advanced adenomas resulting false negatives for these premalignant lesions. Therefore, more accurate, non-invasive screening tools are needed. Here, the utility of analyzing volatile organic compounds (VOCs) in exhaled breath in a FIT positive population to detect the presence of colorectal neoplasia was studied.

METHODS: In this multicenter prospective study breath samples were collected from 382 FIT-positive patients with subsequent colonoscopy participating in the national Dutch bowel screening program (n = 84 negative controls, n = 130 non-advanced adenomas, n = 138 advanced adenomas, and n = 30 CRC). Pre-colonoscopy exhaled VOCs were analyzed using Thermal Desorption - Gas Chromatography - Mass Spectrometry and the data was pre-processed and analyzed using machine-learning techniques.

RESULTS: Using 10 discriminatory VOCs advanced adenomas could be distinguished from negative controls with a sensitivity and specificity of 79% and 70%, respectively. Based on this biomarker profile, CRC and AA combined could be discriminated from controls with a sensitivity and specificity of 77% and 70%, respectively, and CRC alone could be discriminated from controls with a sensitivity and specificity of 80% and 70%, respectively. Moreover, the feasibility to discriminate non-advanced adenomas from controls as well as advanced adenomas was shown.

CONCLUSION: VOCs in exhaled breath can detect the presence of advanced adenomas and CRC in a CRC screening population and may improve CRC screening in the future.