Mortality from colorectal cancer (CRC) decreased significantly in patients who were offered early screening with fecal occult blood testing (FOBT), a large prospective cohort study showed.
Cancer-specific mortality decreased significantly by 14% in patients who underwent early screening for CRC, as compared with a control group that received late or no invitations to participate in screening. Excess mortality decreased by 16% in the exposure group.
The results probably underestimated the true impact of screening with FOBT, as some participants in the control group underwent testing, reported Johannes Blom, MD, PhD, of the Karolinska Institutet in Stockholm, and co-authors in . Clinicians and patients now have greater confidence that CRC screening reduces the risk of dying of CRC.
"Our study finally confirms the efficacy of the older RCTs [randomized controlled trials] in a population-based routine screening program," Blom told 鶹ý in an email. "Evaluating effectiveness in an ongoing program has previously been very methodologically challenging."
More than a third of patients in the experimental arm did not participate in CRC screening. Learning more about outcomes in patients who were actually screened will provide more insight into the true value of screening.
"We plan for the analyses, as well as comparison with other studies," said Blom. "Evaluating the effectiveness among participants is actually one of the methodological challenges, as there is a self-selection of more healthy individuals with a lower risk of CRC participating in screening. Choosing a comparison group without bias is very difficult. We have evaluated the intervention of invitation to screening in a public health perspective and can demonstrate an effect regardless of participation or not by individuals."
Studies have shown that CRC screening with FOBT reduces cancer-specific mortality. Population-based screening programs have been implemented worldwide, but the magnitude of routine screening's effectiveness in reducing CRC mortality has remained unclear.
The lack of data from large observational studies contributed to initiation of an investigation in 2008 in the Stockholm-Gotland region of Sweden. Conducted from January 2008 through December 2021, investigators in the study recruited individuals born from 1938 through 1954 (ages 60-69).
For data analysis, participants in the intervention arm were invited early (2008-2012) to participate in annual or biennial screening. The screening technology switched from guaiac FOBT to the newer fecal immunochemical test (FIT) in 2015.
The control arm comprised individuals who did not receive invitations to undergo CRC screening and those invited to late screening (2013-2015). The primary outcome was screening impact on CRC mortality in patients who participated in early screening versus those who participated late or not at all.
Data analysis covered Dec. 12, 2022 to June 25, 2023 and included 379,448 people, 203,670 in the exposure group and 175,778 in the control group. Screening participation averaged 63.3%, and participants had a maximum follow-up of 14 years. Follow-up averaged 10.8 years in the screened group and 12.8 years in the control group.
Investigators found that 834 deaths from CRC occurred in 2,190,589 person-years in the exposure group and 889 CRC deaths in 2,249,939 person-years in the control group. In the control group, 34.2% of participants never received an invitation to participate in screening, and 115,616 received an invitation for at least one round of screening.
Individuals who underwent screening early had a 4% reduction in the risk of CRC mortality (95% CI 0.88-1.06), which increased to 14% after adjustment for years of follow-up and attained age (95% CI 0.78-0.95). Women had a significantly lower CRC mortality as compared with men (RR 0.67, 95% CI 0.61-0.74). Investigators found no significant interaction between sex and screening group.
Among individuals with CRC, the experimental arm had 14,573 person-years and 1,160 deaths from all causes versus 15,102 person-years and 1,283 deaths from all causes in the control group. The difference represented a 6% reduction in excess mortality in the experimental arm, increasing to 16% after adjustment (95% CI 0.75-0.93).
Of the 834 CRC deaths in the experimental arm, 435 participants had CRC diagnoses more than 2 years after the last screening invitation. Of the remaining 399 CRC deaths, 204 participants participated in the last round of screening that preceded their diagnosis.
The results support current clinical guidance for CRC screening.
"From a public health perspective, we demonstrate that the older guaiac-based FOBT decreased CRC mortality when used in organized routine screening, and countries without the laboratory resources of FIT should not wait but consider starting population-based screening," said Blom.
Disclosures
The study was supported by the Swedish Cancer Society, Swedish Research Council, and Region Stockholm.
The authors reported having no relevant relationships with industry.
Primary Source
JAMA Network Open
Blom J, et al "Routine fecal occult blood screening and colorectal cancer mortality in Sweden" JAMA Netw Open 2024; DOI: 10.1001/jamanetworkopen.2024.0516.