Screening With a DNA Blood Test to Address Colorectal Cancer Inequities

Colorectal cancer (CRC) screening participation is suboptimal and associated with inequities in CRC outcomes by race/ethnicity and socioeconomic position. A novel, cell free DNA (cfDNA) blood test has potential to increase participation, but has not been studied in groups at highest risk for adverse CRC outcomes. Among patients age-eligible for colorectal cancer screening, not up-to-date, we propose a 2-arm, pragmatic, randomized controlled trial comparing offers of standard screening options (at home fecal immunochemical test (FIT) or colonoscopy) vs. offers of expanded options (at home FIT, colonoscopy, or in clinic cfDNA plus at home FIT), set at a large Federally Qualified Health Center serving individuals at increased risk for inequities in CRC outcomes. Results will inform guideline and policy makers on whether cfDNA should be supported as a screening option, and support planning for a large-scale trial examining impact of a cfDNA option for screening on CRC and advanced neoplasia detection.

Sex

All

Minimum age

45 Years

Maximum age

75 Years

Inclusion Criteria:

1. Persons, aged 45 to 75 years old
2. Not up-to-date with screening, defined based on an existing electronic health record (EHR)-based flag that indicates absence of FIT within the last 12 months, colonoscopy within the last 10 years, sigmoidoscopy within the last 5 years or multi-target stool DNA (Cologuard) test within 3 years.
3. Attending primary care visits during the 2 months of recruitment. According to routine practice, screening status will be confirmed by primary care providers as part of routine visits.
4. Being provided the informed consent form.

Exclusion Criteria:

1. Personal history of colorectal cancer (CRC), adenomas, or other related cancers.
2. Prior history of colorectal surgery
3. Family history of CRC, defined as having one or more first-degree relative (parent, sibling, or child) diagnosed with CRC at any age.
4. Up-to-date with colorectal cancer screening, defined as:

   * Fecal occult blood test (FOBT) or FIT within the last 12 months
   * FIT-DNA (Cologuard) or FIT-RNA (Colosense) test within 3 years
   * cfDNA (Shield) within the last year
   * CT colonography within the last 5 years
   * Sigmoidoscopy within the last 5 years
   * Colonoscopy within the last 10 years
5. Abnormal FIT, FOBT, cfDNA, FIT-DNA, or FIT-RNA test within the last 3 years.
6. Personal history of any of the following high-risk conditions for colorectal cancer:

   * Inflammatory Bowel Disease (IBD), including chronic ulcerative colitis (CUC) and Crohn's disease
   * Familial adenomatous polyposis (FAP)
   * Other hereditary cancer syndromes including but not limited to:

     * Hereditary non-polyposis colorectal cancer syndrome (HNPCC) or "Lynch Syndrome", Peutz-Jeghers Syndrome, MUTYH Polyposis (MAP), Familial Adenomatous Polyposis (FAP), Cowden's Syndrome, Juvenile Polyposis, Serrated Polyposis Syndrome
7. Uninsured patients will be excluded because of inability to ensure follow up. Because of recently expanded Medi-Cal eligibility, exclusions due to insurance are expected to be minimal.

• BACKGROUNDGupta S, Halm EA, Rockey DC, Hammons M, Koch M, Carter E, Valdez L, Tong L, Ahn C, Kashner M, Argenbright K, Tiro J, Geng Z, Pruitt S, Skinner CS. Comparative effectiveness of fecal immunochemical test outreach, colonoscopy outreach, and usual care for boosting colorectal cancer screening among the underserved: a randomized clinical trial. JAMA Intern Med. 2013 Oct 14;173(18):1725-32. doi: 10.1001/jamainternmed.2013.9294. PMID 23921906
• BACKGROUNDSingal AG, Gupta S, Tiro JA, Skinner CS, McCallister K, Sanders JM, Bishop WP, Agrawal D, Mayorga CA, Ahn C, Loewen AC, Santini NO, Halm EA. Outreach invitations for FIT and colonoscopy improve colorectal cancer screening rates: A randomized controlled trial in a safety-net health system. Cancer. 2016 Feb 1;122(3):456-63. doi: 10.1002/cncr.29770. Epub 2015 Nov 4. PMID 26535565
• BACKGROUNDGupta S, Miller S, Koch M, Berry E, Anderson P, Pruitt SL, Borton E, Hughes AE, Carter E, Hernandez S, Pozos H, Halm EA, Gneezy A, Lieberman AJ, Sugg Skinner C, Argenbright K, Balasubramanian B. Financial Incentives for Promoting Colorectal Cancer Screening: A Randomized, Comparative Effectiveness Trial. Am J Gastroenterol. 2016 Nov;111(11):1630-1636. doi: 10.1038/ajg.2016.286. Epub 2016 Aug 2. PMID 27481306
• BACKGROUNDSingal AG, Gupta S, Skinner CS, Ahn C, Santini NO, Agrawal D, Mayorga CA, Murphy C, Tiro JA, McCallister K, Sanders JM, Bishop WP, Loewen AC, Halm EA. Effect of Colonoscopy Outreach vs Fecal Immunochemical Test Outreach on Colorectal Cancer Screening Completion: A Randomized Clinical Trial. JAMA. 2017 Sep 5;318(9):806-815. doi: 10.1001/jama.2017.11389. PMID 28873161
• BACKGROUNDLieberman A, Gneezy A, Berry E, Miller S, Koch M, Ahn C, Balasubramanian BA, Argenbright KE, Gupta S. Financial Incentives to Promote Colorectal Cancer Screening: A Longitudinal Randomized Control Trial. Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1902-1908. doi: 10.1158/1055-9965.EPI-19-0039. Epub 2019 Aug 6. PMID 31387970
• Lieberman A, Gneezy A, Berry E, Miller S, Koch M, Argenbright KE, Gupta S. The effect of deadlines on cancer screening completion: a randomized controlled trial. Sci Rep. 2021 Jul 6;11(1):13876. doi: 10.1038/s41598-021-93334-1.