Current and future colorectal cancer screening strategies

Abstract

Despite strong evidence of effectiveness, colorectal cancer (CRC) screening remains underused. Currently, there are several options for CRC screening, each with its own performance characteristics and considerations for practice. This Review aims to cover current CRC screening guidelines and highlight future blood-based and imaging-based options for screening. In current practice, the leading non-invasive option is the faecal immunochemical test (FIT) based on its high specificity, good sensitivity, low cost and ease of use in mailed outreach programmes. There are currently five blood-based CRC screening tests in varying stages of evaluation, including one that is currently sold in the USA as a laboratory-developed test. There are ongoing studies on the diagnostic accuracy and longitudinal performance of blood tests and they have the potential to disrupt the CRC screening landscape. Imaging-based options, including the colon capsule, MR colonography and the CT capsule, are also being tested in active studies. As the world attempts to recover from the COVID-19 pandemic and adapts to the start of CRC screening among people at average risk starting at age 45 years, non-invasive options will become increasingly important.

Fig. 1. Images of a sessile serrated lesion on colonoscopy and a sessile serrated lesion on CT colonography.

a | Sessile serrated adenoma on colonoscopy. b | CT colonography image of a serrated polyp; note contrast covering the surface. Note these are not the same lesion, but the images demonstrate that these lesions are indeed flat and can be detected by the adherence of mucus and contrast material on the surface of the polyp. Part b reprinted with permission from ref., Elsevier.

Fig. 2. CRC screening tests in development.

For blood-based tests, there are at least six blood-based colorectal cancer (CRC) screening tests in various stages of development. These tests range from CRC-specific tests to multi-cancer early-detection tests. Candidate analytical targets include cell-free DNA (cfDNA), methylated circulating tumour DNA (ctDNA), including the gene-specific methylated septin 9 (mSEPT9), and combinations of methylated DNA and proteins. Multi-omics tests use a combination of methylated DNA and protein and apply an artificial intelligence and/or machine learning (AI/ML) classifier to sort populations of individuals into ‘positive’ or ‘negative’ for cancer or advanced neoplasia. For imaging-based tests, in addition to CT colonography described in Fig. 1, other imaging-based tests in development include the colon capsule, a CT capsule of the colon and MR colonography. MR colonography image reproduced from ref. with permission from BMJ Publishing Group Ltd. Colon capsule image reprinted with permission from ref., Copyright © 2015 AGA Institute. Published by Elsevier Inc. CT capsule image reproduced from ref. with permission from BMJ Publishing Group Ltd.