Multitarget stool DNA testing for colorectal-cancer screening.

By T. Imperiale, D. Ransohoff, S. Itzkowitz, T. Levin, P. Lavin, G. Lidgard, D. Ahlquist, B. Berger. New England Journal of Medicine, 2014

1,662 citations recorded by the source corpus.

BACKGROUND An accurate, noninvasive test could improve the effectiveness of colorectal-cancer screening. METHODS We compared a noninvasive, multitarget stool DNA test with a fecal immunochemical test (FIT) in persons at average risk for colorectal cancer. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation, and β-actin, plus a hemoglobin immunoassay. Results were generated with the use of a logistic-regression algorithm, with values of 183 or more considered to be positive. FIT values of more than 100 ng of hemoglobin per milliliter of buffer were considered to be positive. Tests were processed independently of colonoscopic findings. RESULTS Of the 9989 participants who could be evaluated, 65 (0.7%) had colorectal cancer and 757 (7.6%) had advanced precancerous lesions (advanced adenomas or sessile serrated polyps measuring ≥1 cm in the greatest dimension) on colonoscopy. The sensitivity for detecting colorectal cancer was 92.3% with DNA testing and 73.8% with FIT (P=0.002). The sensitivity for detecting advanced precancerous lesions was 42.4% with DNA testing and 23.8% with FIT (P<0.001). The rate of detection of polyps with high-grade dysplasia was 69.2% with DNA testing and 46.2% with FIT (P=0.004); the rates of detection of serrated sessile polyps measuring 1 cm or more were 42.4% and 5.1%, respectively (P<0.001). Specificities with DNA testing and FIT were 86.6% and 94.9%, respectively, among participants with nonadvanced or negative findings (P<0.001) and 89.8% and 96.4%, respectively, among those with negative results on colonoscopy (P<0.001). The numbers of persons who would need to be screened to detect one cancer were 154 with colonoscopy, 166 with DNA testing, and 208 with FIT. CONCLUSIONS In asymptomatic persons at average risk for colorectal cancer, multitarget stool DNA testing detected significantly more cancers than did FIT but had more false positive results. (Funded by Exact Sciences; ClinicalTrials.gov number, NCT01397747.).

Subfields: Oncology, Pathology and Forensic Medicine, Surgery

View Paper: https://www.semanticscholar.org/paper/e51236797e90a3fe94e2cfb413cb4bc8482102c7

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Citations in the corpus

Early detection of cancer (2022, positive): “A prominent example of a successful multimodal cancer detection test combines an assay for fecal blood with a test for known cancer-associated DNA mutations, for improved colorectal cancer screening ( 84 ) over the single fecal hemoglobin test and is now in clinical use.”
Colorectal cancer screening for average‐risk adults: 2018 guideline update from the American Cancer Society (2018, methodology): “The best evidence for the performance of mt-sDNA testing comes from a large, manufacturer-funded, multicenter, comparative trial of mt-sDNA and FIT testing in averagerisk individuals using colonoscopy as the reference standard.(103) The sensitivity of mt-sDNA for CRC was 92.”
ACG Clinical Guidelines: Colorectal Cancer Screening 2021. (2021, background): “By extension, it is appropriate to exclude positive mtsDNA colonoscopies from the routine ADR calculation because the test includes a FIT (182).”
Large-scale pancreatic cancer detection via non-contrast CT and deep learning (2023, neutral): “38), and low-dose CT for lung cancer, with a PPV of 3.8% (ref.”
Global Cancer Incidence and Mortality Rates and Trends—An Update (2015, methodology): “A noninvasive stool DNA test has also been developed and was recently approved by the US Food and Drug Administration (FDA) (24, 25).”
Global cancer statistics, 2012 (2015, background): “Elsewhere in Asia, high incidence rates are observed in a number of provinces in South-Eastern China, including Guangdong and Hong Kong, and in other parts of Southern Asia (the Philippines, India, and Thailand).(40,41) Rates are also elevated in Micronesia/”