In this study, we analysed the characteristics of organised CRC screening programmes that have been performed in 58 countries or areas worldwide. The screening using faecal tests or colonoscopy as the primary screening test was associated with a greater reduction in mortality, followed by faecal tests or FS, FIT only, gFOBT or FIT, and gFOBT only. Moreover, the CRC-related morality was also influenced by screening duration. The pooled ASMRs of mortality reduction in the FIT screening subgroup showed a decreasing trend with a longer duration of screening implementation. Additionally, we found that programmes with gFOBT only as a primary screening test had a limited impact on mortality reduction in males and females. The sensitivity analysis also supported our result that screening strategy offers faecal test or colonoscopy as a primary screening test showed a significant reduction in ASMR in comparison with gFOBT.

Existing evidence suggests that FIT had better performance than gFOBT due to the higher participation rate and higher detection rate of CRC [12, 13]. Our study indicated that the organised screening with the FIT was associated with a greater reduction in mortality (16.7%) than those with gFOBT (4.4%) as the primary screening test, which was consistent with previous research. A network meta-analysis reported that FIT reduced 59% of CRC-related mortality, while gFOBT only reduced CRC mortality by 14% [14]. Gini and colleagues reported about 8–16% of the decline in mortality attributable to gFOBT and 35–41% of mortality decline due to FIT screening in Europe [15]. The differences in mortality reduction between our study and others might be explained by the variations in screening coverage, screening uptake, people’s attitude to CRC screening, development of novel treatment strategies, and lifestyle modification [16].

Besides these two screening strategies, colonoscopy was found to be associated with a 61–68% decline in CRC-related mortality [14, 17, 18]. However, few countries or areas are equipped with adequate resources to offer colonoscopy as a primary test in CRC screening programmes. Furthermore, some countries offered colonoscopy as an alternative option for a primary screening test. We reported that the screening with faecal tests or colonoscopy as a primary screening test had the best performance (42%) among CRC screening modalities. Among this subgroup, the Czech adopted faecal tests or colonoscopy for eligible participants aged above 50 years, while colonoscopy alone was offered to the high-risk population in Israel [19, 20]. A tailor-made screening strategy by risk was recommended by the Asia–Pacific Working Group on Colorectal Cancer, and they adopted the Asia–Pacific Colorectal Screening score to stratify individuals according to the risk of advanced neoplasia [21].

CRC screening programmes tend to have a time lag to observe the benefit, as it often takes years for symptoms to appear or before death occurs. The United States Preventive Services Task Force indicated that it should take at least seven years to observe the benefit of CRC screening [22]. Another survival meta-analysis estimated that it took about 4.8 years to prevent one CRC-related death per 5000 participants screened [23]. In our study, we found a non-significant ASMR of mortality reduction in screening programmes implemented with a duration of less than five years, which may imply the existence of the time lag effect of CRC screening. However, when the duration of screening implementation exceeded five years, we found that all subgroups had significant ASMRs of mortality decrease and that the length of duration was significantly associated with lower mortality. A longer duration of screening might extend a larger screening coverage and have a higher uptake rate, which could be translated to a more obvious mortality reduction in the general population.

Owing to the consideration of the programme surveillance and quality control, we only included organised screening in this study. Opportunistic screening requires a well-developed primary care system that may contribute to a reduction in CRC-related mortality, for example, in the US, where had fallen its CRC-related mortality in these two decades. However, it may reduce the cost and gain more effectiveness if organised screening is adopted. Although there is no cost-effectiveness analysis (CEA) in the US to compare the outcomes of organised and opportunistic CRC screening programmes, there was a CEA that supported organised cervical cancer screening in another developed area (Hong Kong) [24]. Moreover, organised screening could help to remain the equity of access in cancer screening [25]. Also, organised screening has a higher uptake rate than opportunistic screening. For example, Germany implemented the opportunistic screening programme and introduced colonoscopy as a primary screening test, but the participation rate was suboptimal [26]. Researchers suggested introducing organised screening to replace opportunistic screening to improve adherence [27, 28].

This study has some strengths. This study firstly reviewed the long-term impact of all organised CRC screening programmes on CRC-related mortality from a global perspective. In addition, we extracted the mortality of people over 50 years of age rather than the general population, as most CRC screening was initiated at the age of 50 years, which is more appropriate to observe the benefit of CRC screening. Moreover, we also observed the mortality changing in relation to the screening duration with the time lag effect of mortality. Also, the linear mixed model was used in this study to test the robustness as a sensitivity analysis. Nevertheless, some limitations should be addressed. First, our mortality reduction rates are different from that of previous studies, which may be due to the existence of potential confounders. These include people’s attitude to CRC screening, changes in lifestyle habits over time, and the development of novel cancer treatments that were not able to be accounted for, although a study from the US suggested that only 12% of mortality decline was attributed to treatment [29]. Second, the rollout process and uptake were not controlled for in this study, hence we excluded the pilot programmes from pooled estimates and conducted subgroup analyses according to the duration of screening implementation.

In conclusion, CRC screening programmes with a duration of implementation for over 5 years had an association with CRC-related mortality reduction, and the primary screening strategy which provides an option of faecal tests vs. colonoscopy is recommended for countries with adequate health resources. As the duration of programme implementation plays a role, we suggest formulation of a sustainable, organised CRC screening programme as soon as possible in countries where the burden of cancer is likely to increase substantially in the near future.