Contemporary trends and survival outcomes in young-onset vs. average-onset metastatic colorectal cancer: A real-world comparison.

e15614 Background: Colorectal cancer (CRC) is the third most common cancer worldwide. It is a major cause of morbidity and mortality, typically affecting individuals over 50 years (average-onset CRC, AO-CRC). However, the incidence of young-onset CRC (YO-CRC), diagnosed before age 50, has been rising and now accounts for 10-12% of CRC cases. It is also alarming that YO-CRC present with advanced stages and by 2030 the incidence of YO-CRC is projected to increase by 90%. This study aims to evaluate sociodemographic characteristics and survival differences between YO-CRC and AO-CRC with metastasis. Methods: We conducted a multi-center retrospective cohort study using data from the TriNetX network, which aggregates de-identified electronic health records from millions of patients across multiple healthcare organizations. Patients diagnosed with primary metastatic CRC were identified using ICD-10-CM codes. Cohorts were stratified into YO-CRC (ages 18-49) and AO-CRC (ages 50-100). Patients with secondary CRC and stage 0-III disease were excluded. Propensity score matching (1:1) was performed for gender, race/ethnicity, comorbidities, and CRC risk factors. The primary outcome was 5-year survival. Descriptive statistics summarized baseline characteristics and multivariate regression and Kaplan-Meier survival analysis assessed survival outcomes. Statistical significance was defined as p < 0.05. Results: At baseline, the YO-CRC cohort included 978 patients and the AO-CRC cohort included 13,475 patients. YO-CRC had a median age of 35.4 ± 6.93 years compared to 63.7 ± 11.8 years in AO-CRC (p < 0.0001). A higher proportion of YO-CRC patients were female (51.7%, p < 0.0001), while AO-CRC was predominantly male (51.6%, p = 0.0003). The YO-CRC and AO-CRC cohorts were primarily non-Hispanic (51.9%, 49.2%) and White (47.7%, 50.1%). Propensity matching (1:1) included 971 matched pairs in each cohort. AO-CRC patients had a significantly higher 5-year mortality risk (RR 1.282, 95% CI: 1.151,1.427). Likewise, Kaplan-Meier survival analysis showed significantly better 5-year survival of 46.7% in YO-CRC patients and 33.7% in AO-CRC patients (log-rank test p < 0.0001). The median survival time was 4.35 years for YO-CRC and 2.67 years for AO-CRC independent of treatment, indicating a survival advantage in the younger cohort. Conclusions: Metastatic YO-CRC is associated with better survival outcomes compared to metastatic AO-CRC after adjusting for confounders, despite a more aggressive clinical disease profile in younger patients. This trend may be influenced by differential biological, molecular and clinical factors. Our findings emphasize the need to consider age-related differences in survival and investigate tailored treatment strategies for younger patients with CRC. It also highlights whether CRC screening guidelines should be further changed to optimize timely diagnosis.