Blood-based colorectal cancer screening: are we ready for the next frontier? (2024)

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Blood-based colorectal cancer screening: are we ready for the next frontier? (1)

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Lancet Gastroenterol Hepatol. Author manuscript; available in PMC 2023 Oct 1.

Published in final edited form as:

Lancet Gastroenterol Hepatol. 2023 Oct; 8(10): 870–872.

Published online 2023 Jul 21. doi:10.1016/S2468-1253(23)00188-7

Christina P Wang, Sarah J Miller, Aasma Shaukat, Lina H Jandorf, David A Greenwald, and Steven H Itzkowitz

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The publisher's final edited version of this article is available at Lancet Gastroenterol Hepatol

The discovery of circulating and cell-free tumour DNA in the blood has ushered in new possibilities for blood-based colorectal cancer screening.1 The septin 9 test is currently the only US Federal Drug Administration-approved blood-based colorectal cancer screening test that is available; however, due to its low sensitivity, this test was not included in the 2021 US Preventive Services Task Force Recommendation for colorectal cancer screening.2 Two other blood-based tests are being developed with the goal of early detection of colorectal cancer or its precursors. One test applies machine learning and multiomics to cell-free DNA (NCT04369053) and the other test uses a multimodal approach to detect circulating tumour DNA (NCT04136002). CancerSEEK (Exact Sciences, WI, US) and Galleri (GRAIL, CA, US) are multicancer early detection tests that have both shown over 80% sensitivity for colorectal cancer in initial studies;1 Galleri is currently available in the USA, although not reimbursable by insurance.1 Enthusiasm for the burgeoning collection of non-invasive screening tests has been met at the US federal level. The Centers for Medicare & Medicaid Services has already established predefined metrics for test validity and society endorsem*nts, before extending widespread coverage for blood-based biomarkers.3 We might be on the brink of a transformative era in colorectal cancer screening, where blood-based testing is poised to disrupt the field.

Non-invasive screening strategies, such as blood-based biomarkers, offer viable approaches to meet the increased demand for colorectal cancer screening. Patients have consistently expressed a preference for non-invasive colorectal cancer screening strategies, even predating the COVID-19 pandemic.4,5 Additionally, in one study, in which individuals were randomly assigned to receive a blood-based or stool-based test for colorectal cancer screening, adherence to a blood-based test was 11% greater.6 National initiatives in the USA, such as 80% in Every Community and President Biden’s Cancer Moonshot, underscore the public health imperative to address millions of screenings delayed by COVID-19, and to rectify long-standing screening disparities that have disproportionately affected minority, immigrant, rural, and socioeconomically disadvantaged communities. Blood-based tests could potentially help screen millions who are currently unscreened.

However, enthusiasm for blood-based tests needs to be cautious. Our fragmented health-care systems are not currently equipped to handle programmatic screening and might suffer from confusion and decision fatigue with the addition of yet another non-invasive test. Second, like stool-based tests, blood-based biomarkers must be understood as a two-step screening test, where a positive or abnormal blood test (first step) will necessitate a follow-up colonoscopy (second step). Our current experience with stool-based tests and rates of follow-up colonoscopy shows serious gaps in completing the second step. Patients should complete a timely follow-up colonoscopy (within 6 months) given the elevated cancer risk in these circ*mstances, yet it is completed in only half of cases, and much less so across safety-net health settings providing health care to publicly insured or uninsured patients.7,8 Health systems should consider this disturbing disparity a call to action.

Colonoscopy completion can be an arduous endeavour, fraught with barriers at the system level, provider level, and patient level that can hinder its execution.9 Within and across health organisations, processes for coordinating follow-up of abnormal stool tests are often unstructured or fragmented. The need for prior insurance authorisations and gastroenterology preprocedure assessments can exacerbate colonoscopy delays. Misattribution of abnormal tests to competing causes or prioritisation of more immediate health concerns might hinder provider efforts. Patient-related obstacles include varying comprehension of bowel preparation instructions, concerns regarding absenteeism from work or care of dependents, transportation limitations, and language differences.9

Is it time to add one more test to our screening menu? With blood-based testing on the horizon, there is now a crucial need to design and operationalise workflows to ensure completion of the important second step of a colonoscopy. There are frameworks for success in this regard. Beginning in 2006, Kaiser Permanente (Oakland, CA, USA) instituted several organisational changes to increase colonoscopy completion following an abnormal faecal immunochemical test, and in doing so, achieved colonoscopy completion rates of 83% by 2016.10 The establishment of a centralised database to monitor abnormal faecal immunochemical test results, alongside streamlined patient outreach and clear delineation of departmental and personnel responsibilities, played a fundamental role in their success. Although strategies for change will vary across regions and health systems, the methods for reviewing institutional behaviours and implementation of models for improvement can be replicated by any organisation. Mixed-methods analyses will be necessary to incorporate vantage points at multiple levels, and should include leadership, health-care providers, nurse coordinators, patient navigators, schedulers, and community stakeholders.10 Triangulating partnerships between primary care, gastroenterology, and population health will be especially meaningful in transforming these perspectives and generating pathways for success, as well as metrics for assessment.

From a policy standpoint, it is important to designate second-step colonoscopy completion as a quality indicator. Given its effect on patient outcomes and organisational performance, establishing this benchmark as the standard of care will encourage health systems to review their current processes and initiate appropriate changes before the mainstream arrival of blood-based colorectal cancer screening. Although the Centers for Medicare & Medicaid Services have only enacted coverage of follow-up colonoscopy after a positive stool-based test this year, it is not yet clear how this legislation will unfold following abnormal blood-based biomarkers.11 In the interim, refocusing our efforts to address the persistent but growing issue of incomplete two-step colorectal cancer screening should be deemed a priority for every health system. We must ask ourselves: are we ready for the next frontier?

Acknowledgments

No direct funding was received for this Comment. CPW receives research salary support from the National Cancer Institute of the National Institutes of Health under Award Number T32CA225617. AS receives consulting fees from Freenome and Iterative Health. SHI receives research support from Freenome and Exact Sciences Corporation, and consulting fees from Exact Sciences Corporation and Geneoscopy. All other authors declare no competing interests. The content is solely the responsibility of the listed authors and does not necessarily represent the official views of the funding agencies listed.

Contributor Information

Christina P Wang, Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

Sarah J Miller, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

Aasma Shaukat, Division of Gastroenterology, Department of Medicine, New York University Grossman School of Medicine, New York City, NY, USA.

Lina H Jandorf, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

David A Greenwald, Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

Steven H Itzkowitz, Dr Henry D Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York City, NY 10029, USA.

References

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Blood-based colorectal cancer screening: are we ready for the next frontier? (2024)

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