Colorectal cancer screening programs: how should we improve efficacy?

Colorectal cancer (CRC) has become a global burden for several reasons: costs of treatment, high mortality, and (more recently), because it has become a common disease in different populations and world regions (most prominently due to an increase in prevalence in Asia). This burden stresses the need for preventive measures, such as screening programs, which over many years have been developed in different countries and regions, with differing approaches to the problem but all having morbidity and mortality reduction as the ultimate goal.

“Considering these study results, the question remains: how should we improve the efficacy of screening? A nursery rhyme comes to mind: should we tinker with the general concepts of programs, should we tailor the existing methods for subpopulations, or should we soldier on with new methods?”

In this issue of Endoscopy, an article by Larsen et al. aims to define the pathways for people participating in fecal immunochemical test (FIT) screening programs [1]. FIT programs are already a well-established method for CRC prevention and are widely implemented in many countries worldwide. Larsen et al. focused their interest on the group of screened individuals with positive FIT results but with no findings on colonoscopy (negative colonoscopy). One would assume that the FIT result was a false positive and therefore treat the colonoscopy as the gold standard for CRC and precancerous lesion detection, with the resulting recommendation of a standard 10-year interval, or even longer, after a high quality colonoscopy considered to be safe [2]. However, many countries recommend shorter intervals to the next colonoscopy/FIT. The Danish cohort was analyzed at 8 years’ follow-up, and showed that the CRC risk was lower compared with a non-screened population. However, on closer inspection, the effect was not equal in different age- and sex-related groups, most notably in younger attendees (49–59 years old) and women. These results strengthen the belief that the “one size fits all” approach in FIT screening is not acceptable.

Another well-established CRC screening method is primary colonoscopy. It is not used that widely, mostly due to the high costs of colonoscopy. Recently, however, more robust data have been published on the efficacy of primary colonoscopy. The NordICC trial [3] is a randomized controlled trial comparing primary colonoscopy screening with usual care. The results after 10 years of observation led to the conclusion that primary colonoscopy as a screening program is effective, reducing the risk of CRC, but not mortality. In addition, the risk reduction was lower than anticipated (18%). This observation can be mostly attributed to low participation in screening (ranging from approximately 30% to 60% of invitees, depending on the country). Some could argue that the results do not inform the public on the true potential benefits of primary colonoscopy screening; however, we must remember that when it comes to real-life applications, such a pragmatic approach provides actual assessment of intervention on the population level (invitation to colonoscopy, instead of colonoscopy itself). This observation begs the question of whether primary colonoscopy is indeed a possible means of CRC screening? Data on participation in the screening program in Poland were even less encouraging [4].

Considering these study results, the question remains: how should we improve the efficacy of screening? A nursery rhyme comes to mind: should we tinker with the general concepts of programs, should we tailor the existing methods for subpopulations, or should we soldier on with new methods?

Depending on the screening method, numerous initiatives or solutions have been proposed. For primary colonoscopy, interventions have focused mostly on improving the participation rate and considering organized, invitation-based screening as the only viable option (instead of opportunistic screening); unfortunately, the societal perception of colonoscopy as a cumbersome, invasive, and painful procedure remains. Moreover, the financial and organizational burden needed to provide the population with a mass colonoscopy service exceeds the potential benefits from the healthcare providers’ perspective. When considering FIT screening, interventions have focused mainly on cutoff values for FIT positivity (with lower cutoffs resulting in a higher need for colonoscopy but lower rate of missed CRC) or intervals between tests and/or colonoscopies (one of which is the Dutch analysis of FIT-positive/colonoscopy-negative screenees [1]); however, all these interventions create a picture of FIT screening as tailored for specific populations, making global uniform solutions impossible to create.

DNA testing for CRC has come a long way from the early concept many years ago. Recently, two studies evaluating the sensitivity of different DNA tests (blood- and stool-based) were published [5], and both present very optimistic results regarding specificity not only for CRC, but also for advanced precancerous lesions. In the case of blood testing, a sensitivity of >80% was demonstrated, which may seem a little low; however, we should also consider the ease of use in comparison with stool tests or colonoscopy. On the other hand, stool-based DNA test showed a sensitivity of >90%, making it a reasonable alternative to FIT testing. These publications, especially the blood-based DNA test, may be considered a first step toward applying new CRC screening methods that would overcome issues connected to the currently proposed modalities, paving the way for truly mass use.

Publikationsverlauf

Artikel online veröffentlicht:
11. April 2025

• References

• 1 Larsen PT, Jørgensen SF, Rasmussen M. et al. Colorectal cancer incidence following a negative colonoscopy in fecal immunochemical test-based screening: a nationwide cohort study after 8 years of screening in Denmark. Endoscopy 2025; 57
• 2 Pilonis ND, Bugajski M, Wieszczy P. et al. long-term colorectal cancer incidence and mortality after a single negative screening colonoscopy. Ann Intern Med 2020; 173: 81-91
• 3 Bretthauer M, Løberg M, Wieszczy P. et al. Effect of colonoscopy screening on risks of colorectal cancer and related death. N Engl J Med 2022; 387: 1547-1556
• 4 Pilonis ND, Bugajski M, Wieszczy P. et al. Participation in competing strategies for colorectal cancer screening: a randomized health services study (PICCOLINO Study). Gastroenterology 2021; 160: 1097-1105
• 5 Chung DC, Gray DM 2nd DM, Singh H. et al. A cell-free DNA blood-based test for colorectal cancer screening. N Engl J Med 2024; 390: 973-983
• 6 Imperiale TF, Porter K, Zella J. et al. Next-generation multitarget stool DNA test for colorectal cancer screening. N Engl J Med 2024; 390: 984-993