March is Colorectal Cancer (CRC) Awareness Month, and it highlights a disease that affects millions worldwide. Colorectal cancer is the second-leading cause of cancer-related death in the United States, even though it is highly treatable if caught early. However, the American Cancer Society (ACS) estimates that 154,270 adults will be diagnosed with CRC and 52,900 adults will die from CRC in 2025. Currently, >1 in 3 adults (nearly 50 million Americans) are not following screening recommendations. [1] This screening rate is about 59%, which is below the goal of 80% for eligible individuals set by the ACS’ National Colorectal Cancer Roundtable campaign.
The primary reason my be difficult to pinpoint, however, non-compliance to screening recommendation is often due to the perception that screening, including colonoscopy or stool-based tests, are invasive, unpleasant, or inconvenient. Other factors include a lack of physician recommendation, identification of eligible patients, physician knowledge, understanding and attitudes and inadequate patients counseling.
“A lack of gastroenterologists to conduct colonoscopies in regions with low screening, poor education on the importance of screening, or limited access to other testing methods is expected to be the root cause of the delay in screening. Hence, emphasizing the use of non-invasive testing methods, including blood or stool tests can increase screening and hopefully catch CRC earlier,” explained noted Selena Yu, Senior Medical Analyst at GlobalData, a data and analytics company.
The lack of compliance to screening recommendations indicates that, despite multiple available screening tools, a large part of the eligible population does find these tools appealing (enough) to consider screening.
“Health departments globally need to reevaluate CRC screening programs as more people under the age of 50 are diagnosed with CRC,” Yu noted.
“If more countries follow in the US’ footsteps and drop screening ages to 45 or younger, the CRC test market will expand to accommodate a larger test population. With limited access and potentially long wait times to get colonoscopies, CRC in vitro diagnostics (IVD) tests are necessary to bridge the screening gap,” Yu added.
Recommended screening methods
Currently, in the US, the recommended screening methods by the US Preventative Task Force (USPSTF) are the fecal immunochemical test (FIT), highly sensitive guaiac-based fecal occult blood test (HSgFOBT), a multi-target stool DNA test, also known as a sDNA-FIT (Cologuard), every 1 t 3 years, or visual exams by colonoscopy, computed tomography colonography or flexible sigmoidoscopy every 5 years or flexible sigmoidoscopy once every 10 years in combination with an annual FIT.[2]
Both HSgFOBT and FIT detect blood in the stool. They use, however, different methods. HSgFOBT is based on chemical detection of blood, while FIT uses antibodies to detect blood. [3] Stool DNA tests detect DNA biomarkers for cancer in cells shed from the lining of the colon and rectum into stool.
Currently, the only stool DNA test approved by the US Food and Drug Administration is a multitarget stool DNA test that also includes a FIT component, referred to as sDNA-FIT.
Follow-up with a colonoscopy for further evaluation may be required if a stool-based tests reveal abnormal results. Overall, among the stool-based tests, screening with annual FIT or annual sDNA-FIT provides an estimated greater life-years gained than annual HSgFOBT or sDNA-FIT every 3 years.[4]
Modeling estimates that annual screening with sDNA-FIT would result in more colonoscopies than annual screening with FIT. However, sDNA-FIT every 1 to 3 years is estimated to provide a reasonable balance of life years gained per estimated follow-up colonoscopy compared with no screening.[4][5]
A New test based on a simple blood draw
Since the last update of the recommended screening methods in 2021, a new test, known as the Shield test, a cell-free DNA (cfDNA) blood-based test, also known as a liquid biopsy, developed by Guardant Health for colorectal cancer screening in adults aged 45 years and older who are at average risk for the disease has become available.
The new test not only simplifies colorectal cancer screening, a blood-based test has also the potential to improve screening adherence, detect colorectal cancer earlier, and reduce colorectal cancer-related mortality. However, while Shield was approved by the FDA in July 29, 2024 as a primary screening option and is reimbursable by Medicare, it has not yet been included in the USPSTF recommendations. [6]
Studies
The approval of the Shield test was as based on the outcome of the ECLIPSE clinical study involving more than 20,000 patients evaluating the performance of the test for detecting colorectal cancer in average-risk adults.
The study, conducted in more than 200 study sites in both rural and urban communities across 37 states, was uniquely designed to reflect the diverse population of the United States. Results from the study, published in March 2024 in The New England Journal of Medicine (NEJM), confirmed that Shield demonstrated 83% sensitivity for the detection of colorectal cancer, with 90% specificity for advanced neoplasia. This performance is within range of current guideline-recommended noninvasive screening methods, in which overall colorectal cancer sensitivity ranges from 74% to 92%.[7]
Collaboration in development
The development of the Shield blood test is the result of more than 10 years of research by Guardant Health in collaboration with leading health organizations. Following the availability of a laboratory-developed test version, in May 2022, overall adherence to the Shield test has been more than 90%. In other words, more than 90% of individuals who received the test in a real-world clinical setting, completed it. One of the unique benefits of the test is that physicians can have their patients complete a Shield test with a simple blood draw during a routine office visit.
In comparison with a colonoscopy or (flexible) sigmoidoscopy, which both requires special preparation, dietary changes, time, and discomfort, this new minimally invasive test is more convenient, while, potentially, providing a more comprehensive insight by identifying remnants of tumor DNA released into the circulation. However, Shield is also more convenient when compared with the unpleasantness of handling stool.
“Although stool-based testing is more accessible compared to visual exams like colonoscopies, there is still a lack of uptake from patients. Since the Shield test requires a simple blood draw, this can expand access to care for millions of Americans,” Yu concluded.
“The Shield test is particularly exciting because it’s the first of its kind in the US market, and with reimbursement by Medicare, 45 million Medicare beneficiaries are covered. The goal is with increased screening, more individuals will be diagnosed with CRC earlier when it is the most treatable,” Yu concluded.
Clinical trials
Evaluation of the ctDNA LUNAR Test in an Average Patient Screening Episode (ECLIPSE)
ClinicalTrials.gov ID NCT04136002
Reference
[1] Centers for Disease Control and Prevention. U.S. Cancer Statistics Colorectal Cancer Stat Bite. U.S. Department of Health and Human Services; 2024.
[2] National Center for Chronic Disease Prevention and Health Promotion. Division of Cancer Prevention and Control
[3] Colorectal cancer screening tests. Centers for Disease Control and Prevention. Online. Last accesses on March 18, 2025
[4] Knudsen AB, Rutter CM, Peterse EFP, Lietz AP, Seguin CL, Meester RGS, Perdue LA, Lin JS, Siegel RL, Doria-Rose VP, Feuer EJ, Zauber AG, Kuntz KM, Lansdorp-Vogelaar I. Colorectal Cancer Screening: An Updated Decision Analysis for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2021 May. Report No.: 20-05271-EF-2. PMID: 34097370.
[5] Knudsen AB, Rutter CM, Peterse EFP, et al. Colorectal cancer screening: a collaborative modeling study for the US Preventive Services Task Force. JAMA. 2021;325(19):1998-2011. doi:10.1001/jama.2021.5746
[6] Ranganathan K, Kurian NS, Goswami HM, Rishi KD, Veldore VH. Exploring the clinical utility of liquid biopsy with cfDNA in cancer: A systematic review. J Liq Biopsy. 2024 Mar 20;5:100150. doi: 10.1016/j.jlb.2024.100150. PMID: 40027943; PMCID: PMC11863880.
[7] Chung DC, Gray DM 2nd, Singh H, Issaka RB, Raymond VM, Eagle C, Hu S, Chudova DI, Talasaz A, Greenson JK, Sinicrope FA, Gupta S, Grady WM. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. N Engl J Med. 2024 Mar 14;390(11):973-983. doi: 10.1056/NEJMoa2304714. PMID: 38477985.
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DOI
 Awareness Month, and it highlights a disease that affects millions worldwide. Colorectal cancer is the second-leading cause of cancer-related death in the United States, even though it is highly treatable if caught early. However, the American Cancer Society (ACS) estimates that 154,270 adults will be diagnosed with CRC and 52,900 adults will die from CRC in 2025. Currently, >1 in 3 adults (nearly 50 million Americans) are not following screening recommendations. [1] This screening rate is about 59%, which is below the goal of 80% for eligible individuals set by the ACS' National Colorectal Cancer Roundtable campaign.){kind=link}