How to increase colorectal cancer screening for those aged 45 to 49

The incidence of colorectal cancer (CRC) has shown contrasting trends between younger and older adults. While CRC rates have been declining among older Americans, this encouraging trend is not mirrored in younger populations. Notably, there has been a significant and alarming rise in CRC cases among adults in their 20s and 30s (QH). Early-onset colorectal cancer (EOCRC) in those under 50 now accounts for approximately 10-12% of newly diagnosed CRC cases. Predictions indicate that for individuals born in 1990, the risk of developing CRC is two to four times higher than for those born in 1950 (matched at the same age, i.e. younger than 35). Such trends have sparked discussions about recommending earlier CRC screenings, as forecasts suggest that between 2015 and 2030, CRC incidence in those aged 20-34 could double.

One question is how to maximize colorectal cancer (CRC) screening among average-risk adults aged 45–49. In other words, how to translate trial findings into scalable outreach, operations, cost awareness, and clear metrics so health systems can move quickly to implement the screening. This age group is the most relevant because they are just under the 50 year-old age threshold for CRC screening before 2021.

In 2021, the U.S. Preventive Services Task Force (USPSTF), an independent panel of experts in prevention and primary care, lowered the starting age for average-risk CRC screening to 45, thus triggering coverage under the ACA. As mentioned above, CRC in younger adults has been trending upward, making it a priority to adapt population-health programs—historically built for ages 50–75—to the newly eligible 45–49 cohort. These middle-aged adults are often busy, asymptomatic, and new to the idea of screening, so outreach must be simple, salient, and low-friction from the first touch.

The primary goal is to increase any completed CRC screening within 6 months of outreach. Secondary goals include optimizing the modality mix (home-based FIT vs colonoscopy), reducing time-to-completion, and ensuring timely follow-up after a positive FIT.  Those with high-risk indications (e.g., certain family histories, IBD, prior CRC or adenomas) are excluded from this outreach because they need specially tailored pathways.

Colorectal cancer screening options include stool-based tests and visual exams. The fecal immunochemical test (FIT) is a noninvasive annual test that detects blood in the stool. Multitarget stool DNA testing (FIT-DNA, e.g., Cologuard) combines FIT with molecular markers and is typically done every 3 years. Visual methods directly inspect the colon: colonoscopy (every 10 years if normal) both detects and removes precancerous polyps but requires bowel prep and sedation; flexible sigmoidoscopy views the distal colon (about every 5 years, sometimes paired with FIT); and CT colonography ("virtual colonoscopy") every 5 years images the whole colon without sedation but still needs prep and requires follow-up colonoscopy for abnormal findings. All positive non-colonoscopy tests should be followed by a diagnostic colonoscopy, which is the gold standard.

FIT -- a home-based stool test -- is ideal for mail programs, offers the lowest friction, and repeats annually. Colonoscopy is definitive and required after a positive FIT but is resource-intensive and capacity-dependent. The main focus is on these two screening approaches.

A recent study attempted to address this question by investigating the compliance of eligible patients in a randomized controlled trial. The approximately 20,000 subjects were invited via an electronic patient portal and assigned to one of four groups: (1) Usual-care default mailed FIT outreach -- a portal message stated a FIT kit would be mailed, after which participants received the kit with step-by-step instructions and a prepaid return mailer; (2) FIT-only active choice -- a portal message explained age-eligibility and that FIT is an easy, effective CRC screening method, then required participants to choose between completing a FIT kit or deferring screening; (3) Colonoscopy-only active choice -- a portal message described colonoscopy as an effective screening method and required a choice between colonoscopy or deferring; and (4) Dual-modality active choice -- a portal message presented both FIT and colonoscopy and required a choice among FIT, colonoscopy, or deferring. Each of the groups was assessed on concordance to recommended screening. 

 

Perhaps not surprisingly, researchers found that unsolicited mailed FIT as the default produced the highest 6-month screening (26.2%), significantly outperforming all active-choice arms (~14.5–17.4%, see Figure 1). In the dual-choice arm, colonoscopy use exceeded FIT (12.0% vs 5.6%). Engagement was high (~50% portal access in week 1; ~80% ever), yet only 17–22% of those invited to choose made an explicit choice—underscoring the value of removing steps. Notably, 73% with an abnormal FIT completed colonoscopy within 6 months. For positive FITs, outreach should occur within 7 days and colonoscopy scheduled within ≤8 weeks, aiming to beat a ≥80% completion target at 6 months (slightly higher than the observed 73%).

More surprisingly, roughly 10% of those in the mailed FIT group, had a colonoscopy performed (most instead of the FIT that they received). This number was only slightly smaller than the percentage who completed colonscopy screening in the colonoscopy-only group (Figure 1).

These FIT completion rates were consistent with previous results from another study. O’Leary et al. (2023) found that a real-world mailed-FIT program to newly eligible 45–49-year-olds achieved 17.1% FIT returns in 60 days, and a simple enhanced envelope (padded with tracking label and colored messaging sticker) versus plain envelope boosted returns by roughly 9 percentage points over a plain envelope. 

In summary, default mailed FIT is the recommended starting point: it is low-cost (about $8 per kit), scalable, and maximizes uptake but requires reliable navigation for positives and annual repeats. Interestingly, adding a tracking label and colored messaging sticker to the kit can boost compliance significantly. Active choice respects preferences and raises colonoscopy share but, in 45–49s, tends to lower overall completion compared with a FIT default and relies on portal engagement. Colonoscopy-only can be “one-and-done” for completers but underperforms on total participation. Sequential choice can salvage nonresponders yet may delay completion and shows mixed evidence on net gains.

Figure 1. Percent of participants (x-axis) who completed screening for each of the four groups described above in the main text. The gray dot indicates any screening (FIT or colonoscopy), the dark blue dot represents FIT completed, and the yellow dot is colonoscopy completed. Colonoscopies performed after an abnormal FIT result are not included (reproduced from Galoosian et al. JAMA, 2025).