Reductions in colorectal cancer (CRC) mortalities of 25% in a 14-year follow-up were observed in a population invited vs not invited to take part in a fecal occult blood screening program. The reductions exceeded 40% when focusing specifically on those who underwent the screening.

“The key message [from the findings] is that [CRC] screening saves lives but only if people participate,” first author Johannes Blom, MD, PhD, of the Department of Surgery, Södersjukhuset, Stockholm, Sweden, told Medscape Medical News.

“Our findings suggest that invitation to screening may prevent roughly one quarter of [CRC] deaths, while participation in the screening program may prevent more than 40% of those deaths,” he added.

The study was published online in JAMA Network Open.

Assessment of the efficacy of population-based CRC screening programs can be challenging, with factors such as variable adherence to the screening invitation to development of cancers following the screening period.

To evaluate a screening program in Sweden after adjustment for those and other factors, Blom and colleagues conducted a prospective cohort study of 376,511 individuals aged between 60 and 69 years, including 203,692 individuals who had been invited to undergo fecal occult blood screening tests every 2 years as part of a routine population-based cancer screening program between 2008 and 2012 (study group).

A separate control group included 172,819 patients enrolled between 2013 and 2015 who did and did not receive invitations to screen.

About 49% of participants were male in each group. For those receiving screening, if results were positive, individuals underwent follow-up colonoscopy.

With follow-up analyses conducted from May 2024 to February 2026, there were a total of 856 CRC deaths in the study group and 812 CRC deaths in the control group.

Overall, those who received the screening invitation had a 26% reduction in CRC mortality compared with those who did not receive the screening invitation (mortality rate ratio [RR], 0.74), after adjusting for CRC deaths from cancers diagnosed more than 2 years after the screening test in the study group and for the numerous participants who were invited to receive screening in the control group.

Meanwhile, the average rate of participants who adhered to the invitation and underwent screening was 63%, and after further adjusting for those who were invited but did not undergo the testing, the reduction in CRC mortality between those who did and didn’t test was even greater, at 43% (RR, 0.57).

“A 43% reduction is substantial, especially because it was observed in a routine screening program under real-world conditions rather than in a tightly controlled clinical trial,” Blom said.

In a previous study of the population, Blom and colleagues found only about a 14% reduction in CRC mortality, similar to the 15% reported in original randomized trials for fecal occult blood screening programs.

However, with more than half of the CRC mortalities in the screening group occurring after the screening period ended, along with many in the control group winding up receiving invitations to screen, the estimation of the true reduction of mortalities associated with the screening program was complicated — as is common.

“Importantly, relatively few studies have been able to estimate the effect of actual participation in a routine population-based screening program,” Blom said.

“The main contribution of the new study is that we were able to adjust for these sources of contamination, meaning some screening exposure in the control group and some [CRC] deaths occurring after screening exposure had effectively ended,” he said.

Of note, when the screening program began, guaiac-based fecal occult blood testing was used, with a later transition to fecal immunochemical testing (FIT), and with many participants provided both approaches over time, the tests’ individual effects could not be assessed, Blom said.

Importantly, however, Blom added that regardless of the type of test, the estimate should not be interpreted as the effect of taking a single stool test.

“Rather, it reflects participation in an organized screening program over time, including repeated invitations and the possibility of follow-up colonoscopy when indicated,” Blom said.

“The broader clinical message is that [CRC] screening can substantially reduce the risk of dying from the disease, particularly when people actively participate in the program,” he said.

“The benefit comes from detecting cancers earlier, when treatment is more effective, and from identifying and removing precancerous lesions before cancer develops.”

For clinicians, the practical implication is straightforward, Blom said: “Encouraging eligible patients to participate in screening and to complete recommended follow-up after a positive test may be one of the most effective actions for reducing [CRC] mortality at a population level.”

Adjustment for Confounders Reveals True Impact of Screening

Commenting on the study, Atsushi Sakuraba, MD, PhD, an associate professor and director of RUSH Center for Crohn’s and Colitis, Division of Digestive Diseases and Nutrition, at RUSH University Medical Center in Chicago, said the findings shed important light on the need to adjust for key confounders in research.

“Nonadherence and contamination substantially dilute observed screening effectiveness, making intention-to-screen analyses appear far less beneficial than the true per-protocol effect,” Sakuraba told Medscape Medical News.

“Adjusting for these factors is essential because real-world programs often have mixed exposure patterns that obscure the actual impact of screening.”

Importantly, the study drives home the message that “clinicians should recognize that fecal occult blood testing can reduce CRC mortality by more than 40% when patients actually complete the test as intended,” he said.

Mortality Reductions of 50% in Spain

In separate research on mortality benefits related to a CRC screening program, researchers report substantial mortality reductions associated with a biennial FIT-based screening program in the Basque Country, Spain, with a population of approximately 2.2 million, targeting individuals aged 50-69 years.

The retrospective study tracked mortality trends from 2004 to 2024, showing a 29.6% reduction in age-standardized CRC mortality over the 20 years that included the CRC screening period, which started in 2009.

Among the individuals aged 50-69 years targeted for screening, CRC mortality declined by 50.1% over the study period, from 39.7 to 19.8 deaths per 100,000 population.

“The relevance [of the reductions] is substantial: Achieving a reduction equivalent to 3000 deaths per million inhabitants is extraordinary,” first author Luis Bujanda, MD, PhD, professor of medicine, Department of Liver and Gastrointestinal Diseases, Biogipuzkoa Health Research Institute-Donostia University Hospital, University of the Basque Country, San Sebastián, Spain, told Medscape Medical News.

While the study wasn’t designed to stratify between those who did and did not undergo the screening, a significant inflection point in CRC mortality was importantly identified in 2012, 3 years after screening was implemented.

As many as 70.8% of screen-detected CRCs were diagnosed at stage I or II, which is consistent with evidence on early-stage diagnoses with screening programs.

While the study didn’t stratify mortality based on participants and nonparticipants, Bujanda noted that the findings are consistent with the team’s previous research suggesting a nearly 80% reduction in CRC-related mortalities associated with FIT participants over 10 years, compared with nonparticipants.

Based on the collective findings, “it is a failure of governments and policymakers not to implement organized [CRC] screening programs,” Bujanda said. “Clinicians should advocate for their establishment and for transparency in reporting program outcomes.”

Blom and Sakuraba had no disclosures to report. Bujanda reported receiving personal fees from Norgine and Alfasigma during the conduct of the study.