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  • Review Article
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Novel colorectal cancer screening methods — opportunities and challenges

Nature Reviews Clinical Oncology volume 22, pages 581–591 (2025)Cite this article

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Abstract

Globally, colorectal cancer (CRC) is the second leading cause of cancer death and the third most common incident cancer. CRC begins as adenomatous or serrated polyps, and in particular as advanced precursor lesions (APLs), which have the potential to progress into invasive cancers. Screening for CRC facilitates early detection and can identify cancers more amenable to cure, and can also detect and remove precursor lesions, thus also preventing CRC. Colonoscopy is the mainstay of screening in the USA and has the distinct advantage of enabling both detection and removal of precursors lesions. However, colonoscopy is burdensome, expensive and invasive, and often has negative findings. Non-invasive tests, such as testing stool samples for biomarkers of risk, have the potential to identify individuals who are more likely to benefit from colonoscopy. From a public health perspective, improving compliance with screening remains a priority. Technological innovations, including the emergence of new markers to improve stool testing and the development of blood tests that examine cell-free DNA have the potential to improve screening uptake and effectiveness. The trade-off between uptake of screening testing, detection of cancer and important precursor lesions such as APLs, and costs make for a complex calculus. In this Review, we describe the current state of CRC screening and evaluate the risks and benefits of new developments in screening.

Key points

  • On a population level, the effectiveness of colorectal cancer (CRC) screening is highly dependent on the extent of screening uptake.

  • Colonoscopy enables direct visual inspection of the entire colon and therefore provides the highest level of sensitivity and specificity for CRC screening, although this procedure is also burdensome and expensive, which limits uptake.

  • Colonoscopy facilitates CRC prevention by enabling the identification and removal of precursor lesions as part of the same procedure, whereas a positive non-invasive stool or blood test requires follow-up colonoscopy.

  • Stool-based tests offer a convenient, effective alternative to colonoscopy, although abnormal test results must be followed up with colonoscopy.

  • Blood-based assays provide sensitive methods of CRC detection but are much less sensitive for advanced precursor lesions. Owing to this limitation, blood-based tests are less effective than colonoscopy and stool-based testing for screening.

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Fig. 1: Sensitivity and specificity of screening methods for the detection of colorectal cancer.
Fig. 2: Sensitivity of screening methods for the detection of advanced precursor lesions.

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  1. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Melina A. McCabe & Anthony J. Mauro

  2. Division of Gastroenterology, Hepatology and Nutrition, Departments of Medicine and Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    Robert E. Schoen

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R.E.S. has acted as an adviser of Guardant and has received research funding from Exact Sciences, Freenome and Immunovia. M.A.McC. and A.J.M. declare no competing interests.

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McCabe, M.A., Mauro, A.J. & Schoen, R.E. Novel colorectal cancer screening methods — opportunities and challenges. Nat Rev Clin Oncol 22, 581–591 (2025). https://doi.org/10.1038/s41571-025-01037-7

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