Simple SummaryColorectal cancer is becoming more common in adults under 50. This trend has been observed worldwide, the reasons for which are unclear. Research has suggested that young patients present with more advanced diseases compared to their older counterparts yet have similar survival. How young patients respond to current treatments is unknown as they represent a small proportion of studies to date. The aim of this study is to evaluate disease-specific features and survival of patients diagnosed with colorectal cancer under 50 years of age. Increased understanding of the characteristics of early-age onset colorectal cancer will help to design age-specific preventative, diagnostic, and treatment strategies for these patients and to inform public health policies and initiatives.AbstractBackground:The incidence of colorectal cancer (CRC) is increasing in the young (under 50). Defining the clinicopathological features and cancer-specific outcomes of patients with early-onset CRC is important to optimize screening and treatment strategies. This study evaluated disease-specific features and oncological outcomes of patients with early-onset CRC.Methods:Anonymized data from an international collaboration were analyzed. The inclusion criteria for this study were patients aged <50 years with stage I-III disease surgically resected with curative intent. Overall and disease-free survival were calculated using the Kaplan–Meier method.Results:A total of 3378 patients were included, with a median age of 43 (18–49) and a slight male preponderance (54.3%). One-third had a family history of colorectal cancer. Almost all (>95%) of patients were symptomatic at diagnosis. The majority (70.1%) of tumors were distal to the descending colon. Approximately 40% were node positive. Microsatellite instability was demonstrated in one in five patients, representing 10% of rectal and 27% of colon cancers. A defined inherited syndrome was diagnosed in one-third of those with microsatellite instability. Rectal cancer displayed a worse prognosis stage for stage. Five-year disease-free survival for stage I, II, and III colon cancer was 96%, 91%, and 68%, respectively. The equivalent rates for rectal cancer were 91%, 81%, and 62%.Conclusions and relevance:The majority of EOCRC would be captured with flexible sigmoidoscopy. Extending screening to young adults and public health education initiatives are potential interventions to improve survivorship.