February's Paper of the Month looks at the benefits and harms of colorectal cancer (CRC) screening using primary colonoscopy or fecal immunochemical testing (FIT) compared with usual care with no screening.
Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial - Westerberg M, Ludvigsson JF, Metcalfe C, Strömberg U, Blom J, Engstrand L, Hellström M, Löwbeer C, Steele R, Holmberg L, Forsberg A. Nat Med. 2026 Feb 20. doi: 10.1038/s41591-026-04225-9
What is known about the subject
The American College of Gastroenterology and the European Society of Gastrointestinal Endoscopy recommend CRC screening in individuals aged 50–75 years, using either colonoscopy or FIT, with colonoscopy reserved for individuals at increased risk, as indicated by a higher faecal haemoglobin level.
The Swedish SCREESCO RCT trial included a primary colonoscopy screening arm and two rounds of a two-stool FIT screening arm with an unusually low cut-off point (10 μg/g faeces), as well as a control arm comprising individuals who were not invited for screening but received usual care.
The aim of the present study was to assess whether screening approaches resulted in a higher rate of CRC diagnosis, particularly of stages I–II, during the diagnostic phase compared to usual care. It also aims to assess potential harms of screening approaches in terms of an increased rate of cardiovascular and gastrointestinal events in general and short-term all-cause mortality.
What the study adds
278,280 individuals aged 60 years were included, 31,113 individuals were assigned in the primary colonoscopy arm, 60,267 in the FIT×2 arm and 186,671 primary colonoscopy controls, of whom 120,521 were also controls for comparison with the FIT×2 arm.
After a median follow-up of 4.8 years, the incidence rate of CRC was 107.9 in the colonoscopy arm and 99.9 in controls per 100,000 person-years (incidence rate ratio (IRR): 1.08, 95% confidence interval (CI): 0.91–1.28) and 96.0 in the FIT arm and 103.9 in controls (IRR: 0.92, 95% CI: 0.81–1.05).
The incidence rate of diagnosed stage I–II CRCs in the primary colonoscopy arm was 58.7 per 100,000 person-years compared to 42.5 in the control arm (IRR: 1.38, 95% CI: 1.09–1.74). Similarly, the rate in the FIT×2 arm was 52.7 and 44.4 in FIT×2 controls (IRR: 1.19, 95% CI: 0.99–1.43).
At the end of follow-up, the incidence rate of cardiovascular events was similar in all arms. The rate of gastrointestinal events was somewhat higher in the FIT×2 arm compared to the control arm also at the end of follow-up, primarily iatrogenic bleeding (IRR: 1.18, 95% CI: 1.05–1.32) and unspecified gastrointestinal bleeding (IRR: 1.14, 95% CI: 1.04–1.26).
Implications for colorectal practice
- There was an increase of stage I–II CRC incidence in the intervention arms compared to usual care, particularly during the first year after randomisation when most of the screening colonoscopies were performed.
- More stage I–II and fewer stage III–IV CRCs were diagnosed in the intervention arms compared to controls after a median follow-up of almost 5 years.
- Rates of gastrointestinal or cardiovascular events were higher in the first year and later on more similar to usual care.
- The increase in CRC detection implies a benefit of screening.
References
- Săftoiu, A. et al. Role of gastrointestinal endoscopy in the screening of digestive tract cancers in Europe: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. Endoscopy 52, 293–304 (2020).
- Shaukat, A. et al. ACG clinical guidelines: colorectal cancer screening 2021. Am. J. Gastroenterol. 116, 458–479 (2021).
- Castells, A. et al. Effect of invitation to colonoscopy versus faecal immunochemical test screening on colorectal cancer mortality (COLONPREV): a pragmatic, randomised, controlled, non-inferiority trial. Lancet 405, 1231–1239 (2025).
- Robertson, D. J. et al. Baseline features and reasons for nonparticipation in the colonoscopy versus fecal immunochemical test in reducing mortality from colorectal cancer (CONFIRM) study, a colorectal cancer screening trial. JAMA Netw. Open 6, e2321730 (2023)