CRC Screening by Colonoscopy and FIT Improves Early Detection over Usual Care

Screening detects more cases of colorectal cancer at an early stage, according to new research based on data from over 278,000 Swedish 60-year-olds. While other studies have shown the benefits of screening, this one was unusual as it included patients who underwent one of two interventions or no screening at all (usual care). The interventions were colonoscopy or fecal immunochemical testing (FIT) followed by colonoscopy if indicated.

The study, which is a collaboration between Uppsala University and Karolinska Institutet, has been published in Nature Medicine. The lead author is Marcus Westerberg, PhD, docent at Uppsala University and also the study’s author for correspondence.

“SCREESCO is unique since it has three arms—a primary colonoscopy arm, FIT arm and a control arm. The other ongoing randomized trials besides SCREESCO that include both primary colonoscopy and FIT are the Spanish COLONPREV trial and the U.S. CONFIRM trial. These do not include a usual-care control arm,” senior author Anna Forsberg, PhD, told Inside Precision Medicine. She is docent at Karolinska Institutet, and head of the SCREESCO study.

She added that, “Other related trials include trials on sigmoidoscopy and FOBT-based screening. Primary sigmoidoscopy trials have shown reduced CRC incidence and earlier-stage detection, but comparable evidence for FIT-based screening is limited.” 

Cancer of the colon and rectum, or colorectal cancer (CRC), is one of the most common cancers in the elderly, and has recently become a leading cancer among those under 40 as well, although screening is usually only recommended after age 50. Early detection is therefore crucial to reducing hospitalization and mortality. However, colonoscopies have a notoriously low rate of uptake. 

This is an urgent need in medicine, and it has led to the development of new technologies, such as other fecal tests from Exact Sciences—Cologuard and Cologuard Plus, and Guardant’s blood based screening test—Guardian Shield. The world market for CRC screening was valued at approximately $15–$18 billion in 2025 and is projected to reach over $27–$57 billion by 2033–2034.  

In this new study, researchers at Karolinska Institutet and Uppsala University investigated whether screening with colonoscopy or FIT, followed by colonoscopy if indicated, could effectively catch early stage CRC.

The study involved over 278,000 people who were randomly offered either a primary colonoscopy; two fecal immunochemical tests (FIT), where the patients provided a stool sample, which was followed by a colonoscopy if one of the samples was positive; or no intervention at all—termed usual care.

Both types of screening led to more detection of early-stage cancers being detected, especially in the first two years, which is when most of the interventions were carried out. Usually, cancer diagnosed early is more likely to be successfully treated. For CRC, it is also possible to detect and remove adenomas—precursors that might otherwise have developed into cancer.

The SCREESCO study started in 2014. Participants were 60 years old, identified via the population register, and then randomized into the three different groups: primary colonoscopy, fecal immunochemical test, and offered a follow up colonoscopy if they had a positive test, or usual care—participants did not undergo either intervention but acted as a control group.

When precursors to cancer were found in a colonoscopy, patients received treatment according to the current guidelines, such as polyp removal. The participants were then followed via the register until 2020.

The researchers found that the number of cases of more advanced colorectal cancer had decreased in both intervention groups. The clearest results were seen in the group where the participants had done FITs. Among these patients, 0.61 percent developed colorectal cancer, compared to 0.73 percent in the control group. 

“We can show that cases of advanced cancer tend to decrease towards the end of the period in the group that was randomized to provide stool samples for FIT. This could be evidence of a preventive effect of the screening, through the removal of the precursors to cancer,” said Forsberg.

The study also investigated whether there were any negative effects associated with an increased number of colonoscopies. The researchers were able to see a slight increase in stomach and intestinal bleeding as well as blood clots in these patient groups, especially in the first year when most of the colonoscopies were performed. However, these events were unusual, and the all-cause mortality rate was the same in all groups.

The researchers now plan to follow the participants in the study until 2030 to see how effective the different screening methods are in reducing long-term mortality from colorectal cancer.

“This study gives us great hope that screening will also be shown to reduce mortality from colorectal cancer in both groups when the study is finally evaluated in about five years,” said Forsberg.

Westerberg added, “Key remaining questions for improving CRC screening include clarifying the long‑term comparative benefits of FIT versus colonoscopy versus usual care, determining the extent of overdiagnosis with early-stage cancers and missed cancers (post colonoscopy CRCs), and identifying optimal FIT strategies such as cut-off levels.”

There is great interest in the impact emerging technologies could have.    

“Cologuard and Cologuard Plus tests are both well established, non-invasive stool-based screening tests that are part of the USPSTF guidelines and that out-performed FIT in their clinical trials. For example, in the BLUE-C trial, which was recently published in the New England Journal of Medicine, the updated version of the multitarget stool DNA (mt-sDNA) stool test [Cologuard plus] had a Stage 1, 2 or 3 sensitivity for CRC of 92.7% compared to 64.6% for FIT,” Jordan Karlitz, FACG, AGAF, told Inside Precision Medicine. He is principal screening medical officer, Exact Sciences.

“Over 54 million Americans today remain unscreened due to the time and hassle associated with colonoscopies and unpleasantness of handling stool-based tests. As physicians, we know the best test is the one that gets done. Shield is preferred by patients and physicians for this reason and has been proven to increase screening participation in the real-world,” Guardant Health’s chief medical officer, Craig Eagle, MD, told Inside Precision Medicine.

He adds, “Multiple research studies through the years continue to show how critical early detection is for survivorship against colorectal cancer, including a 91% chance of survival when detected early.”

Foster is cautious though, and said, “Emerging screening technologies—such as next‑generation multitarget stool DNA tests and blood‑based cell‑free DNA assays—are showing promise but currently do not outperform FIT or colonoscopy.”