Fecal volatile organic compounds for early detection of colorectal cancer: where are we now?

INTRODUCTION: The fecal volatolome, which is composed of fecal volatile organic compounds (VOCs), seems to hold potential as non-invasive biomarker for the detection of colorectal cancer (CRC) and its precursor lesions advanced adenomas (AA). The potential of the fecal volatolome has been subject of various studies using either chemical analytical or pattern-recognition techniques. The available literature on the potential of the fecal volatolome as CRC and AA biomarker was reviewed. METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, Google Scholar and ResearchGate using the following keywords: Colorectal Cancer, Advanced Adenoma, Volatile Organic Compound, Metabolome, Gas Chromatrography-Mass Spectrometry, Selected-Ion Flow-Tube Mass Spectrometry, eNose, and Fecal Biomarkers. RESULTS: Eighty-eight titles or abstracts were identified from the search, of which 11 papers describing the potential of the fecal volatolome for CRC detection were selected. In these studies, different techniques were used for the headspace analyses of fecal VOCs, limiting the possibility to compare outcomes. Increased levels of amino acids and short chain fatty acids, and decreased levels of bile acids and polyol alcohols in the gas phase of feces were observed repeatedly. All selected papers reported high diagnostic value for the detection of both CRC and AA based on fecal VOCs. CONCLUSION: Based on the included studies, fecal VOC analyses seem promising for future screening of CRC and AA, with potentially improved test performances allowing for earlier detection of AA and CRC and consequently earlier initiation of treatment, possibly reducing morbidity and mortality rates next to lower rates of (unnecessary) colonoscopies.

The scent of colorectal cancer: detection by volatile organic compound analysis.

The overall metabolic state of an individual is reflected by emitted volatile organic compounds (VOCs), which are gaseous carbon-based chemicals. In this review, we will describe the potential of VOCs as fully noninvasive markers for the detection of neoplastic lesions of the colon. VOCs are detected by our sensory olfactory nerves and form the molecular basis for our sense of smell. As such, we emit our own individual odor fingerprint or so-called smellprint. This may change over time in response to any alteration in metabolism such as modifications caused by gastrointestinal infection, inflammation, external factors such as medication and diet, or development of neoplastic disease such as colorectal cancer. This means that analysis of VOCs can provide a fully noninvasive metabolomics biomarker profile that could be used as a diagnostic tool. Thus far, canine scent detection, gas chromatography-mass spectrometry, and electronic nose technologies allow for discrimination between patients with and without colorectal cancer and also its precursor (advanced adenoma) with promising accuracy. The challenge for future research is to identify specific biomarkers driving these signals. This enables the development of primed sensors tailored toward accurate identification of volatiles specific to colorectal cancer and adenomas. Such a technique may allow noninvasive monitoring of response to therapy and could revolutionize screening practices for colorectal cancer and potentially many other gastrointestinal diseases.

Higher fecal immunochemical test cutoff levels: lower positivity rates but still acceptable detection rates for early-stage colorectal cancers.

BACKGROUND: Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC). METHODS: Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL. RESULTS: In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from ≥ 50 to ≥ 200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively. CONCLUSIONS: Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present. IMPACT: Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers.