In 2020, 1.9 million new colorectal cancer (CRC) cases and 935,000 related deaths occurred worldwide1, mostly from metastatic disease. In the United States (US), approximately 20% of CRC patients have distant disease at presentation, resulting in an age-adjusted rate of stage IV CRC of 8.9/100,0002. Of patients treated with curative intent for colorectal cancer, a further 20-30% will develop recurrent disease3. Despite substantial transformation in the care of stage IV colorectal cancer including advances in chemotherapy and its delivery, targeted molecular and immune therapies, increased use of hepatic and pulmonary metastectomy, and increasingly aggressive approaches to peritoneal metastases, treatment for patients with late-stage disease remains less effective and more expensive, and survival remains poor.

Colorectal cancer is considered a disease of developed countries and its incidence correlates strongly with the Human Development Index. The highest age-standardized rates occur in Northern Europe. In Hungary, Slovakia, Norway, Denmark, and the Netherlands CRC incidence exceeds 40/100,000. The lowest rates occur in Asia and Africa. Burkina Faso, Guinea, Gambia, Bangladesh, and Bhutan have rates <4/100,0003. However, rates in developing countries are increasing rapidly as lifestyle changes and risk factor exposure increases. Because of this, the global burden of disease is expected to increase dramatically and in countries without screening capacity, many patients will present with late-stage disease.

Overall, rates of colorectal cancer have fallen in highly developed countries thanks to uptake of screening and removal of adenomatous polyps. From 2000-2014, CRC rates in the United States fell from 54.5/100,000 to 38.6/100,000 with most profound drops in more recent years2. However, these overall gains mask a concerning increase in CRC incidence among adults under 50 years of age. Alarmingly, stage IV disease is being diagnosed with increasing frequency in these younger age groups. From 1995-2015, the average annual percentage of distant disease increased by 2.9% (95% CI, 2.4 -3.4) among US adults ages 40-49, as compared to a 1.3% increase in local disease (95% CI, 0.7-1.9) resulting in statistically significant shift in stage distribution, with distant cases increasing in proportion from 21.7 to 26.6% (p <0.01).5 Increasing incidence has been observed in multiple highly developed countries from 2008-2012. The steepest annual percentage increases in all-stage CRC in young adults occurred in Korea (4.2%, 95% CI 3.4-5.0%) and New Zealand (4.0%, 95% CI 2.1-6.0%)6. These numbers indicate the benefits of screening may not be shared across younger birth cohorts in the future and that surgeons and oncologists worldwide will confront larger numbers of young adults with distant disease.