Short summary

Colorectal cancer is one of the most common occurring cancers in the western world. To combat a high incidence and mortality screening has been initiated in many countries over the last decade. In Denmark a nationwide program arose in 2014. Much of the underlying evidence on long term screening outcomes is based on three trials, one Danish, from the 1980s and 1990s. The purpose of this study is to assess the long term outcomes by using the data collected in the 1980s and 1990s. 

Rationale

Colorectal cancer (CRC) is one of the most common cancers in Denmark, leading to approximately 1.400 deaths annually. The CRC incidence in Denmark is approximately 3.000 cases per year. The current 1 year-survival of CRC is 80 % and the 5-year survival is 60 %. One way of reducing the risk of death due to CRC is by doing an early detection, or screening, program, targeted at healthy citizens.

Large pilot studies on fecal occult blood (FOB) test based CRC screening were conducted in the late 1980s and the early 1990s in the United States, England and Denmark. The studies included a total of 261.334 participants.

In the US study, based in Minneapolis, MN, 46.551 participants 50 to 80 years of age were randomized to either the screening group (either annual or biannual) or the control group (no intervention). The program was carried out, on and off, from 1975 to 1992. Participants were, to ascertain vital status, followed over the course of a 13 year period. Subsequent analysis revealed reduced CRC mortality among those screened by 33 %. A 30 year follow-up study examining the long-term mortality finds a consisted reduced CRC mortality among those screened of 18 %.

In the greater Nottingham area, England, 152.850 participants aged 45 to 74 were randomized to either a FOB screening group (76.466) or a control group (76.384). Between 1981 and 1991 biannual screenings was offered to all intervention group participants.  CRC mortality was found to be 15 % lower in the screening group. A follow-up study 20 years later finds a 13 % reduction in mortality, but no difference in CRC incidence between the two groups.

On the island of Funen, Denmark, 61.933 participants between 45 and 75 years of age were randomized to either a control or a biannual screening group. All participants submitted one FOB test for analysis. Five screening rounds were held between 1985 and 1995. The study finds a significant reduction in CRC-related mortality of 18% among those screened.

Partly based on these findings a CRC screening program was introduced in Denmark in 2014 inviting the entire population between 50 and 74 years of age. From 2014 to 2017 all eligible inhabitants were gradually invited to participate. After 2017 the screening program will continue biannually. The screening invitation consists of an immunochemical fecal occult blood test (iFOBT). The iFOBT is positive if traces of blood are detected. If the threshold is met the participants will be invited to a colonoscopy, performed in order to detect cancers and polyps.

In 2015 64 % of the invited participants accepted and completed an iFOBT, of which 6,9 % was positive. Colonoscopies were subsequently performed and colorectal cancer was detected in 1125 participants, 54 % of which being early stage cancers (pT1+pT2). In addition, 32 % of the participants had medium or high risk adenomas removed.

The high frequency of detected early stage cancers proves the short-term advantages of the CRC screening program. What is unclear is whether or not the long-term outcomes match the short-term. We seek to investigate this with a follow-up study on the Funen cohort focusing on CRC mortality and long-term effects. One area of interest is the long-term effects of polypectomy, an area of research where evidence for alternative practices may be necessary in the future. Data will be compared to the data from the UK and the US allowing us a larger sample size and the opportunity to increase the strength and credibility of our findings. Both studies were designed in a manner resembling the Danish study back in the 1980s and 1990s, making for high comparability. Our results will hopefully demonstrate the effectiveness of a screening program over the course of time, potentially providing decision makers with the opportunity to take evidence-based decisions regarding the future of the screening program. 

• The aim of the study is to determine the long-term effects of CRC screening.
• A number of sub-studies are expected to be published. Areas of sub-study-interest include:
• The effects of polypectomy.
• The difference in mortality patterns between FOB test false-positive and negative.
• The difference between overall mortality and CRC-related mortality between the groups: 30 year follow-up.
• The mortality of CRC in Denmark, the United States and the United Kingdom 30 years after screening.

Description of the cohort

The cohort consists of all participants in the original Funen trial, totaling 61.933 participants divived equally into intervention and control. All Funen citizens at the time were invited, and 61.933 were randomly selected. All were between the age of 45 and 75 at the time of invitation. 

Data and biological material

The data collected to this study includes register data from the National Patient Register (NPR) and clinical data from the original study accessed through the national archives.  

Collaborating researchers and departments

Department of Gastroenterology, Minneapolis VA Hospital, Minnesota & Department of Medicine, University of Minnesota

• Aasma Shaukat, MD, MPH, FACP, FASGE, AGAF, FACG