Colonoscopy Versus Fecal Occult Blood Test Versus No Screening

A comparative analysis of long-term effects

Background: : Colorectal cancer (CRC) remains a leading cause of cancer-related death. Many of these deaths could be prevented by screening. The German screening program was updated in April 2025, enabling men and women aged 50 and above to choose between fecal immunochemical testing (FIT) once every two years or up to 2 screening colonoscopies (CS) at an interval of 10 years apart. In this study, we compare the expected long-term outcomes for these strategies as well as for a combination of the two, assuming that full use is made of the tests that are offered.

Methods: We used COSIMO, a validated multi-stage simulation model for CRC, to assess expected outcomes assuming full adherence for simulated cohorts of 100 000 men and women aged 50–85. We calculated and compared the expected cumulative numbers of CRC cases and CRC-related deaths with FIT-based screening, colonoscopy-based screening, and no screening.

Results: On the assumption of full adherence, the two screening strategies yielded similar reductions of CRC case numbers (69% for FIT, 77% for CS) and deaths from CRC (82% for both). Even stronger reductions were found if CS at age 50 and 60 was followed by FIT at ages 70, 72, and 74 (81% reduction in CRC cases, 89% reduction in deaths from CRC).

Conclusion: The two screening strategies currently offered in Germany are highly effective to a similar extent. Our analysis yields relevant information for informed choices between the alternative screening offers.

Cite this as: Sergeev D, Heisser T, Hoffmeister M, Brenner H: Colonoscopy versus fecal occult blood test versus no screening: A comparative analysis of long-term effects. Dtsch Arztebl Int 2026; 123: 40–5. DOI: 10.3238/arztebl.m2025.0208

Colorectal cancer (CRC) is the third most common cancer and the second most common cancer-related cause of death both globally and in Germany, where CRC continues to account for more than 20 000 deaths per year (1). A large proportion of CRC cases could be prevented by the use of effective screening (2). The best established and most widely used screening examinations are immunochemical fecal occult blood tests (fecal immunochemical tests [FIT] and screening colonoscopy [SC] (3). CRC screening programs are being established and used in more and more countries (4, 5), most of them offering annual or biennial FIT as primary screening examination, to be followed by SC in the case of a positive FIT result. However, in a few countries, including Germany, FIT and SC are offered as alternative primary screening examinations, between which people can choose based on their preference. In Germany, fecal occult blood test and colonoscopy have been offered as alternative primary screening examinations since 2002 (6) with varying and partly quite complex criteria for eligibility according to age, sex, and screening intervals. Since April 2025, both men and women have been entitled to either up to two SC 10 or more years apart or biennial FIT from the age of 50 years. A switch between the two types of screening is possible, but a switch from SC to FIT is only offered 10 or more years after a negative screening colonoscopy (eSupplement–Table 1) (7).

The choice between the two screening options should be as informed as possible. The aims of this study were therefore to establish and compare the expected long-term outcomes of both screening variants—FIT-based screening and colonoscopy-based screening—and to support informed decision making by persons eligible for CRC screeing.

Methods

Study concept

This study used the Colorectal Cancer Multistate Simulation Model (COSIMO), a validated Markov-based simulation tool. By means of COSIMO, the expected effects of various CRC screening strategies in terms of CRC incidence and CRC mortality (8) were modeled. Based on the results, the expected outcomes of the FIT-based and the colonoscopy-based screening options in the target population of the German CRC screening program were assessed and compared. COSIMO simulates the natural history of CRC by modeling the development and progression of precancerous lesions into preclinical and clinical cancer, as described in detail elsewhere (8) and visually summarized in eSupplement–Figure 1.

Figure 1

Visualization of screening options: The screening examinations over time with full adherence to the three screening strategies investigated

We simulated the expected outcomes for hypothetical cohorts of 100 000 men and 100 000 women followed up from age 50 to age 85 years. The primary endpoints were cumulative numbers of CRC cases and CRC-related deaths, compared between the FIT-based and the colonoscopy-based screening options and a scenario without screening. All simulations were conducted separately for men and women, but results are also presented for the two sexes combined.

Model parameters

The model’s input parameters included prevalence estimates for non-advanced adenomas, advanced adenomas, and preclinical CRC at age 50 years, together with the annual transition rates between no lesion, non-advanced adenoma, advanced adenoma, preclinical CRC, clinically manifest CRC, and death from CRC. Age- and sex-specific transition rates between the various stages of carcinogenesis and their 95% confidence intervals (CI) were derived from the colonoscopy data on approximately four million men and women aged 55 years who had undergone SC between 2002 and 2013 and from national cancer registry data (9, 10, 11), and are provided in eSupplement-Table 2. Owing to the observed consistency across all age groups, the transition rates for the age group 55–59 years were assumed to apply also to the age group 50–54 years. We determined the baseline prevalence of various stages of colorectal neoplasms at age 50 years on the basis of the observed prevalences at age 55 years and these transition rates. The results yielded were consistent with the findings of previous studies in Germany (12). The baseline prevalences are presented in eSupplement-Table 3. Based on the rates of false-negative examination results for polyps and adenomas, as determined by tandem screening colonoscopy (13, 14), we assumed SC sensitivity of 75% for non-advanced adenomas and 95% for advanced adenoma and for preclinical cancer. On the basis of the observed sex-specific variations in FIT sensitivity (15, 16, 17, 18), we assumed sensitivity for non-advanced adenoma of 15.7% in men and 10.7% in women, for advanced adenoma of 31.3% in men and 26.3% in women, and for preclinical CRC of 80.6% in men and 75.6% in women. Specificity was assumed as 92.3% in men and 94.7% in women (18).

Annual mortality rates after CRC diagnosis, classified by type of detection (screening, other), were estimated from the data of a large cohort of patients with CRC in a population-based case–control study from Germany and on German registry data (19, 20), and are detailed in eSupplement-Table 4. Data on general mortality rates and life expectancy were sourced from German life tables and are provided in eSupplement-Table 5 (21). Further details on model structure and data sources, including an overview of all parameters, are provided in the eSupplement.

Modeled strategies

We conducted simulations for CRC screening on the assumption of full adherence to the various screening options, with separate simulations for men and women. In order to limit complexity and enhance clarity and communicability, we focus our analyses on perfect adherence to either the FIT-based screening option, with biennial FIT between the ages of 50 and 75 years, or the colonoscopy-based screening option, with SC at ages 50 and 60 years, the latter either with (“combined SC and FIT strategy”) or without (“SC-only strategy”) subsequent biennial FIT-based screening from age 70 to 75 years, when SC is no longer offered. Simulations assuming no screening were run for comparison. The three modeled screening variants are visualized in Figure 1.

Simulations began at age 50 years and were run in annual steps up to age 85 years. It was assumed that positive FIT results were always followed by diagnostic colonoscopy within the same year. Individuals with false-positive FIT results (no findings at colonoscopy) were assumed to resume FIT screening after a 10-year interval. Neoplastic polyps detected on colonoscopy were assumed to be excised, with follow-up surveillance colonoscopy scheduled every 3 years for advanced adenomas and every 10 years for non-advanced adenomas (22).

Outcome measures

For each of the modeled cohorts, we determined the cumulative number of conducted FIT and SC, the number of CRC cases detected early by screening, the remaining cases of CRC (i.e., those not detected by screening), total CRC cases, and deaths from CRC occurring between the ages of 50 and 85 years. Furthermore, we calculated the proportionate reduction in CRC cases and deaths from CRC compared with the cohort without screening. In addition, we estimated the average number of screening FIT, SC, and follow-up procedures per person in each cohort, along with the relative and absolute risk reduction for CRC and death from CRC between ages 50 and 85 years.

Results

CRC incidence and mortality

Over a 35-year observation period, all screening strategies substantially reduced CRC incidence and mortality compared with no screening. Depending on the screening strategy selected, incidence was reduced by 69–81% and mortality by 82–89% overall (Table 1, Figure 2, Figure 3). The combined SC and FIT strategy achieved the greatest reduction in CRC incidence, followed by the SC-only and FIT-only strategies. In addition to the effects of CRC prevention, all screening strategies also led to earlier detection of a substantial proportion of the pre-existing cases of CRC. For the FIT-based screening strategy, more than half of the remaining (i.e., not prevented) CRC cases are expected to be detected early by screening (Figure 2).

Figure 2

Cumulative number of CRC cases between the ages of 50 and 85 years in cohorts of 100 000 men (a) and 100 000 women (b).

Figure 3

Cumulative number of deaths from CRC between the ages 50 and 85 years in cohorts of 100 000 men (a) and 100 000 women (b).

Table 1

Summary of the modeling results for cohorts of 100 000 men and women: population-related perspective

CRC mortality reduction was likewise greatest with the combined SC and FIT strategy, and slightly stronger with the use of SC only than with FIT only. Slightly greater reductions in men than in women were observed for all strategies except combined SC and FIT, for which the results were essentially the same in both sexes.

Individual person perspective

The FIT-based strategy resulted in the highest number of test events, with an average of seven FIT per person (six for men, nine for women) and two colonoscopies between ages 50 and 75 years. In both the colonoscopy-only strategy and the combined colonoscopy and FIT strategy, men and women each had on average three colonoscopies (Table 2). In the combined strategy, men had one FIT on average, and women had two. The absolute risks of CRC diagnosis and of death from CRC were lowest in the combined cohort. The risk of developing CRC dropped from 1 in 10 without screening to 1 in 50 with combined screening. The risk of dying from CRC decreased from 1 in 22 to 1 in 196. All screening strategies reduced the CRC risk substantially, with the combined approach showing the greatest benefit.

Table 2

The modeling results for cohorts of 100 000 men and women: individual participant perspective

Discussion

Our study demonstrates that Germany’s updated alternative options for primary CRC screening, either biennial FIT or up to two SC from the age of 50 years on, have the potential to substantially reduce CRC incidence and mortality. With universal adherence, both the FIT-based strategy and the colonoscopy-based strategy could prevent the vast majority of CRC cases and deaths from CRC between ages 50 and 85 years. Again assuming full adherence, the colonoscopy-based screening strategy would be expected to achieve a slightly greater reduction in CRC incidence, whereas the two screening strategies would be expected to achieve similar reductions in CRC mortality. The strongest reductions in both incidence and mortality would be expected with the combined strategy, i.e., two SC at 50 and 60 years of age, followed by FIT at 70, 72, and 74 years. This strategy, though not explicitly recommended in guidelines, is possible within the framework of the current screening options.

The results of our simulations are in line with previous modeling studies showing that both FIT- and colonoscopy-based screening strategies may reduce CRC incidence and mortality substantially (23). The preventive effect and safety of SC have recently been confirmed for the first time by a randomized controlled trial (24). The lower effect estimates reported from this trial (incidence reduction 18%, 95% confidence interval [7; 30] and 31% [17; 45] in intention-to-screen and per-protocol analysis, respectively; mortality reduction 10% [–16% to 36%] and 50% [23; 73] in intention-to-screen and per-protocol analysis, respectively) may be explained by the later start (55–64 years), the offer of just one SC, the low adherence (42%), contamination by non-screening colonoscopies and the short follow-up (25). Another recently performed randomized controlled trial confirmed FIT-based screening to be non-inferior to SC (26).

Our results provide important model-based estimates to help men and women from the age of 50 years decide among the various screening options. Given the roughly comparably strong effects of the FIT-based and colonoscopy-based screening strategies, individual choices between them may primarily rest on additional factors such as personal preference. From a public health perspective, high adherence to (at least) of the two strategies will be the decisive factor in reducing the burden of CRC, a disease that continues to account for more than 20 000 deaths each year in Germany. In our analyses we modeled scenarios of maximal adherence to reflect the greatest achievable effects, with the aim of enhancing the information on which medical and policy decisions are based. If the offer of alternative options for screening serves to increase the use of effective screening overall, it will make a very useful contribution to the effective prevention of CRC (6).

Nevertheless, overall utilization of CRC screening in Germany continues to lag behind the much higher adherence rates that meanwhile have been achieved in a number of countries with well organized screening programs, such as the Netherlands, Denmark, Australia, and the USA. In the USA, CRC screening has been strongly advocated for several decades, and the incidence of CRC in the age groups eligible for screening has declined by more than one third since the 1990s (4, 5, 27). Although both age standardized CRC incidence and absolute CRC case numbers have also distinctly decreased in Germany since screening colonoscopy was made available in 2002 (28), a major renewed increase in absolute case numbers is to be expected in the decades to come owing to demographic changes (29). Against the backdrop of limited personnel capacity in the health care system and steadily rising cancer treatment costs, this underlines the importance of finding new ways to enhance the use of effective screening strategies.

The strengths of our analysis include use of a validated and fully transparent simulation model, whose main parameters, including all transition probabilities were derived from large national databases. The principal limitations are those shared with other modeling studies: uncertainties regarding potential changes in key model parameters, e.g., alterations in risk factor profiles in younger generations and potential progress in early detection and treatment of CRC. In fact, observations of increases in CRC risk in younger birth cohorts (30), possibly due to risk factor changes such as an increase in the prevalence of overweight and obesity, suggest that the absolute reductions in the numbers of cases and deaths achieved by screening could even be greater than suggested by our modeling results. This further underlines the high public health potential of the enhanced use of effective CRC screening options.

Experience from other countries and the findings of randomized trials show that much higher use of CRC screening can be achieved by means of well organized screening programs with repeat personal invitations and measures to make the screening as simple as possible, such as direct mailing of stool tests or offers of colonoscopy appointments (5, 31, 32). Germany should follow other countries in giving high priority to further development of the CRC screening options to create a well organized screening program. Furthermore, additional research should explore the potential for broadening the screening options, such as implementation of risk-based screening or the offer of a third SC at the age of 70 years.

Funding

This study was supported by grants from German Cancer Aid (nos. 70114735, 70115864) and the German Federal Ministry of Education and Research (no. 01KD2104A).

Data sharing statement

All relevant data used for this modeling study are presented transparently in the article or the supplementary material. The model source code is available at https://www.dkfz.de/en/klinepi/download/index.html.

Conflict of interest statement
The authors declare that no conflict of interest exists.

Manuscript received on 15 July 2025, revised version accepted on 29 October 2025

Corresponding author
Prof. Dr. Hermann Brenner

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