Background
Colorectal cancer remains one of the leading causes of cancer death in the United States. It is especially important in communities with fewer healthcare resources, where people are more likely to miss recommended screening. Screening can find cancer earlier, and it can also prevent cancer by detecting and removing precancerous polyps. For adults aged 45 to 75 years who are due for screening, there are several accepted options, including stool-based tests and colonoscopy.
This study evaluated two mail-based outreach strategies used in community health centers, where many patients face barriers such as transportation issues, limited time off work, language barriers, and reduced access to specialty care. The goal was to see which mailed approach led to better screening participation in real-world primary care settings.
Study Design and Setting
The CARES pragmatic cluster randomized clinical trial was conducted in community health centers in the greater Boston area and Los Angeles County, with an additional nonrandomized parallel site in Rapid City, South Dakota. The trial enrolled English- or Spanish-speaking primary care patients aged 45 to 75 years who were due for colorectal cancer screening.
This was a pragmatic trial, meaning it was designed to reflect routine clinical practice as closely as possible rather than an idealized research setting. That makes the findings especially useful for community health centers and public health programs.
Patients at the randomized sites were assigned to one of two outreach strategies. One group received a mailed fecal immunochemical test, or FIT, along with automated text message reminders from study staff. The other group received a mailed FIT-DNA test, also called stool DNA testing, using the manufacturer’s standard outreach protocol. In Boston and Los Angeles, patients with an abnormal result on either stool test were offered standardized navigation to colonoscopy, which means staff helped them understand the next steps and arrange diagnostic follow-up.
What Are FIT and FIT-DNA?
FIT is a simple stool test that checks for hidden blood in the stool, which can be a sign of colorectal cancer or advanced polyps. It is inexpensive, easy to complete at home, and typically repeated every year if negative.
FIT-DNA testing, sometimes known by the brand name Cologuard in the United States, looks for both hidden blood and abnormal DNA markers shed by cancerous or precancerous cells. It is also done at home, but it is generally used less frequently than FIT and may have a higher one-time detection rate for some lesions. However, a positive result still requires follow-up colonoscopy.
Who Participated?
A total of 5,127 participants were included in the randomized regions of the trial. Of these, 2,435 were in the FIT group and 2,692 were in the FIT-DNA group. The average age was 54.5 years, and just over half were women. The population reflected the communities served by these health centers: 74.5% were Hispanic, 7.2% were non-Hispanic Black, 14.9% were non-Hispanic White, and 1.1% identified as another race.
The study also included many patients facing access barriers. About two-thirds preferred Spanish, nearly half were covered by Medicaid, and 12% were uninsured. These details matter because outreach interventions often work differently depending on language, insurance status, and local healthcare infrastructure.
Main Findings
The primary outcome was whether patients completed any colorectal cancer screening within 90 days, using FIT, FIT-DNA, or colonoscopy. The study also examined screening within 180 days and the time it took patients to complete screening.
Screening participation was significantly higher in the FIT-DNA group than in the FIT group. At 90 days, 27.9% of patients in the FIT-DNA group completed screening compared with 22.6% in the FIT group. At 180 days, the gap remained: 31.7% in the FIT-DNA group versus 26.7% in the FIT group.
These results suggest that mailing FIT-DNA with the manufacturer’s outreach process led to modestly better participation than mailing FIT with text-message outreach from study staff. The difference was meaningful at the population level, especially in settings where even small increases in screening uptake can prevent cancers and save lives.
Site Differences
The researchers also found important differences between regions. In Boston, screening participation at 90 days was higher than in Los Angeles. Specifically, 28.4% of patients in Boston completed screening versus 23.1% in Los Angeles. Similar patterns were seen at 180 days.
These site-level differences likely reflect more than just the outreach method. Community health centers differ in staffing, patient navigation resources, local referral systems, specialty care availability, and social conditions affecting patients’ ability to complete follow-up. The findings highlight that mailed screening programs do not operate in a vacuum; local implementation strongly influences outcomes.
Follow-up Colonoscopy After Abnormal Stool Tests
A critical part of any stool-based screening program is making sure patients with abnormal results get colonoscopy promptly. Without follow-up, the benefit of screening is reduced.
Among the 100 participants who had an abnormal stool test result, only 36 completed colonoscopy within 180 days. That means the follow-up rate was 36.0%, which is below what would be considered ideal. Even though navigation support was available, many patients still did not complete diagnostic colonoscopy within 6 months.
This is one of the most important lessons from the trial: screening outreach alone is not enough. Systems must also address the barriers that prevent patients from completing colonoscopy after an abnormal result, such as appointment availability, bowel preparation concerns, transportation, language access, fear, and competing life demands.
Interpretation
The study shows that mailed outreach can improve colorectal cancer screening in community health centers, but the choice of test and the surrounding support system both matter. FIT-DNA produced higher screening uptake than FIT in this trial, though the absolute difference was moderate rather than dramatic.
At the same time, the study reinforces that access to diagnostic follow-up remains a weak point. A positive stool test is not the end of screening; it is the beginning of a necessary next step. If colonoscopy is delayed or never completed, early detection opportunities are lost.
Why This Matters for Community Health Centers
Community health centers care for many people who are uninsured, underinsured, or facing social and language barriers. These centers often serve as the frontline for preventive care in underserved populations. A practical mailed outreach program can help reach patients who might not otherwise come in for preventive visits.
This trial suggests that a mailed FIT-DNA strategy may be more effective than mailed FIT with automated text reminders in some community settings. However, FIT-DNA tests are often more expensive than FIT, so health centers and payers will need to consider the trade-off between higher uptake and higher cost. Implementation decisions should also account for local capacity to process tests, contact patients, and arrange follow-up colonoscopy.
Clinical and Public Health Implications
The study has several implications. First, outreach methods should be tailored to the patient population and the local care environment. Second, screening programs should not focus only on sending tests; they should also build strong follow-up pathways. Third, bilingual communication and culturally responsive outreach are likely essential in diverse communities.
In real-world practice, a successful colorectal cancer screening program may need several components working together: mailing stool tests, sending reminders, educating patients about the importance of completion, assisting with positive-result follow-up, and reducing logistical barriers to colonoscopy. The CARES trial adds useful evidence that can help community health centers refine these strategies.
Limitations
As with any clinical trial, there are limitations to consider. The study was conducted in specific geographic regions, so results may not be identical in other parts of the country or in different healthcare systems. The populations served by these sites were diverse but also reflected the local communities, which may limit generalizability. In addition, the follow-up colonoscopy outcome indicates that navigation alone may not be sufficient, but the trial does not fully explain all the reasons patients failed to complete diagnostic testing.
Another point is that the comparison was between two different outreach approaches, not only two different tests. The FIT group received automated text reminders from study staff, while the FIT-DNA group followed the manufacturer’s protocol. This means the results reflect both the test type and the implementation strategy.
Conclusion
In this pragmatic cluster randomized clinical trial, mailed outreach improved colorectal cancer screening in community health centers, and mailed FIT-DNA achieved higher participation than mailed FIT. Screening uptake also varied by site, with Boston outperforming Los Angeles. However, follow-up colonoscopy after abnormal stool tests remained suboptimal, even with navigation support.
The study highlights a key reality in preventive cancer care: getting patients screened is only part of the challenge. Ensuring timely diagnostic follow-up is equally important, especially in underresourced settings where colorectal cancer burden is highest.