Background: Colorectal cancer (CRC) is the?second?leading cause of cancer mortality globally.?Varying screening strategies have been implemented in different jurisdictions to limit CRC-associated mortality. The effectiveness of these strategies has not been compared and contextualized in terms of varying background risk, epidemiologic risk?factors?and screening practices.  

Objectives: To evaluate the temporal impact of changing background risk, epidemiologic risk factors, and screening practices on population-level CRC mortality, and to estimate the number of CRC deaths avoided at the country level for males and females associated with these changes. 

Methods: The age-specific population counts and colorectal cancer mortality rates from 1950 to 2019 from 48 countries were estimated using the World Health Organization’s Global Cancer Observatory (GCO) web-based platform. Age-standardized mortality rates (ASMR) were estimated?in 5-year age groups?by sex and country and standardized to the WHO (2000-2025) Standard Population.?Peak mortality was defined as the maximum ASMR (based on a five-year?rolling average). The expected number of colorectal cancer deaths following the peak mortality years were estimated using the peak-year age specific?mortality?rates and age?specific?population?counts?for the index?year.?The total number of avoided deaths were estimated as the difference between the expected and?observed?number of?CRC?deaths in that period.??? 

Results: Amongst those countries who reported sex-specific mortality, there has been a notable reduction (Standardized mortality ratio (SMR) <0.70) in CRC deaths for 7 out of 41 (17.1%) countries for males and only 2 out of 41 (4.9%) countries for females resulting in 1.17 million avoided deaths. Medium reduction (SMR 0.7-0.9) countries were associated with an additional 1.59 million avoided deaths, and low reduction (SMR 0.9-1.0) countries were associated with 0.918 million avoided deaths. These reductions appear to be associated with the implementation of CRC screening programs. In many countries CRC mortality has not yet peaked, which appeared to be associated with westernizing culture trends and slow implementation of CRC screening programs.  

In total, across these 48 countries there has been 2.87 million CRC deaths avoided since mortality rates peaked, with the greatest reductions observed in the US, UK, and Germany. 

Conclusions/ Implications: This study shows the diverging trends in CRC mortality across countries and the progress made in CRC control in reducing cancer mortality. In many countries where CRC screening has been implemented, considerable numbers of CRC deaths have been avoided. The reduction in CRC mortality has not been observed equally for males and females. For many countries CRC mortality rates have not peaked highlighting the importance of further investment in primary and secondary prevention initiatives.