Colorectal cancer (CRC) is the second leading cause of cancer mortality nationally 1. Routine screening for CRC, such as with colonoscopy and fecal immunochemical testing (FIT), at regular intervals leads to earlier CRC detection, lower CRC incidence and mortality, and overall cost savings compared to no screening 2–4. However, there are significant barriers to screening within medically underserved populations (MUP), due in part to cost, accessibility, and acceptability of screening tests. Behavioral Risk Factor Surveillance System (BRFSS) survey data identified low CRC screening rates among patients without healthcare coverage (37%) compared to those with health insurance (69%), as well as lower rates in patients who lack an identifiable healthcare provider (31%) compared to those with a regular provider (69%) 5. Low income and lack of insurance lead to later CRC detection, worse outcomes, and increased mortality from CRC 6.
To date, there are many well-established CRC screening modalities, which can be divided into invasive (capsule endoscopy, sigmoidoscopy, or colonoscopy) or non-invasive testing options (computed tomographic colonography and stool-based testing), and can be further categorized into those detecting polyps versus cancers 7. In the United States, the most utilized method for CRC screening is colonoscopy, but it is not necessarily an ideal screening tool in MUP given its cost, invasiveness, risk, lack of convenience and accessibility, and patient perception 8, 9. To that end, the other modalities remain important alternative screening options. In fact, modeling studies clearly demonstrate that all of the screening methods have benefit over time, and that adherence to testing, regardless of modality, is a key driver for successful screening10. Many people are not up-to-date with CRC screening despite the available testing, with overall screening rates under 70% in the United States in 201811. Some characteristics of a MUP, such as low income, lack of insurance or being underinsured, and lack of a PCP, make screening an even bigger challenge for this group.
FIT has desirable characteristics for the MUP including cost, availability, and efficacy. It has been used frequently for CRC screening in this population, and programmatic FIT has been shown to be effective12. However, return rates are consistently low, around 10%, in MUP compared to the general population13. For MUP without access to a primary care provider who may use health fairs as their principal source of health care, low FIT return rates limit the feasibility of this option.
The Mitchell Wolfson Sr. Department of Community Service (DOCS) is a medical student-run, organization at the University of Miami Miller School of Medicine that provides preventive, primary, and subspecialty care to thousands of MUP in South Florida through various organized activities, including free comprehensive screening health fairs. This patient population is almost exclusively uninsured or underinsured, and a large percentage are not eligible for state or federal programs that facilitate primary care. The county safety net health system affords care for some, but this is mostly in the emergent or urgent settings rather than for elective issues like cancer screening. Therefore, the lone modality of colorectal cancer screening at these fairs has been fecal occult blood testing for many years, initially with guaiac-based and, then, with immune-based testing (FIT), given its affordability. However, we had noted consistently low return and positivity rates of FIT at our health fairs, in line with known national averages13. In the year prior to the data collection presented here, when FIT was the primary CRC screening option offered, 414 patients received FIT but only 52 returned them (12.6%) with 0 being positive (0%).
Blood-based testing presents an opportunity to overcome some, but not all, of the barriers that currently limit screening, particularly in MUP, including ease of use and educational barriers to test use and return. The FDA-approved Septin9 DNA blood test (Epi proColon®) is indicated for screening of patients unwilling or unable to undergo the other recommended tests. This test determines the methylation status of the SEPT9 gene, a member of the Septin family of proteins that bind GTP and act to modulate vesicle trafficking, apoptosis, cytoskeletal remodeling, and cytokinesis14. Hypermethylation of the SEPT9 gene in CRC tissue is associated with colorectal carcinogenesis15 and methylated SEPT9 DNA (mSEPT9) shed from the tumor site is measurable in peripheral blood, providing a blood-based means to test for CRC16,17. Several studies have compared mSEPT9 and FIT testing, and test sensitivity has been found to be comparable across all stages, though at lower mSEPT9 specificity. In one prospective multi-center study, mSEPT9 sensitivity was 73% at a specificity of 80%, compared to 68% at 97% for FIT 18.
Given the potential for a blood-based test to improve screening rates for MUP, we developed a program to assess the impact of adding mSEPT9 testing to our CRC screening station at the DOCS health fairs. Here we report on CRC screening uptake with both mSEPT9 and FIT in MUP and secondarily the performance characteristics of the blood-based test in this resource-limited and ethnically diverse environment.