# Multitarget stool DNA testing for colorectal-cancer screening

Source: https://onco.cc/key-papers/paper-imperiale-multitarget-stool-dna-screening-nejm-2014/  
OnCo record `paper-imperiale-multitarget-stool-dna-screening-nejm-2014` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A stool test that looks for cancer DNA as well as blood found 92 percent of cancers against 74 percent for the blood-only test, at the price of more false alarms. It is the trial behind Cologuard.

## Summary

Imperiale, Ransohoff, Itzkowitz and colleagues compared a non-invasive multitarget stool DNA test with a faecal immunochemical test in people at average risk of colorectal cancer, all of whom also had a colonoscopy. The DNA test includes quantitative molecular assays for KRAS mutations, aberrant NDRG4 and BMP3 methylation and beta-actin, plus a haemoglobin immunoassay, with results generated by a logistic-regression algorithm; values of 183 or more counted as positive, and faecal immunochemical test values above 100 ng of haemoglobin per millilitre of buffer counted as positive. Tests were processed independently of the colonoscopy findings.

Of 9,989 evaluable participants, 65 (0.7 percent) had colorectal cancer and 757 (7.6 percent) had advanced precancerous lesions.

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Tags: colorectal-evidence
- Journal: New England Journal of Medicine
- Year: 2014
- DOI: 10.1056/NEJMoa1311194
- Authors: Imperiale TF, Ransohoff DF, Itzkowitz SH, et al.
- Findings: Sensitivity for colorectal cancer 92.3 percent with the DNA test against 73.8 percent with the faecal immunochemical test (p=0.002).; Sensitivity for advanced precancerous lesions 42.4 percent against 23.8 percent (p<0.001).; Specificity 86.6 percent against 94.9 percent among those with non-advanced or negative findings (p<0.001).; Numbers needed to screen to detect one cancer: 154 with colonoscopy, 166 with the DNA test, 208 with the faecal immunochemical test.
- What it means: The first molecular stool test to reach approval, and the template for the blood tests that followed: more sensitive for cancer, much less specific, and still poor at the precancerous lesions that screening is supposed to remove.
- Caveats: Cross-sectional accuracy against colonoscopy in one round; no trial has shown that stool DNA testing reduces colorectal cancer mortality.; Lower specificity means more colonoscopies per cancer found, which matters where endoscopy capacity is the constraint.; Funded by the test's manufacturer.

## Sources

- N Engl J Med 2014: https://doi.org/10.1056/NEJMoa1311194
- PubMed: https://pubmed.ncbi.nlm.nih.gov/24645800/

## Connected records

- key papers: [Effect of colonoscopy screening on risks of colorectal cancer and related death (NordICC)](https://onco.cc/key-papers/paper-bretthauer-nordicc-colonoscopy-screening-nejm-2022/), [Randomised controlled trial of faecal-occult-blood screening for colorectal cancer (Nottingham)](https://onco.cc/key-papers/paper-hardcastle-nottingham-faecal-occult-blood-lancet-1996/)
- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- fronts: [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- technologies: [Colorectal cancer screening (colonoscopy, FIT, stool DNA, blood)](https://onco.cc/technologies/colorectal-screening/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/)
- drugs: [Cologuard](https://onco.cc/drugs/cologuard/)
- companies: [Exact Sciences (Abbott)](https://onco.cc/companies/exact-sciences/)
- terms: [Faecal immunochemical test (FIT)](https://onco.cc/terms/fit-test/), [Positive predictive value (PPV)](https://onco.cc/terms/ppv/)
- bottlenecks: [Biomarkers are not validated or standardised](https://onco.cc/bottlenecks/b-biomarker-validation/), [The hardest cancers are found late](https://onco.cc/bottlenecks/b-early-detection/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- ideas: [Treat screening uptake, not test sensitivity, as the thing to optimise, and settle the age extension with a trial rather than a model](https://onco.cc/ideas/idea-crc-screening-uptake-and-age-extension/)

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