Treatment Variation Impacts Survival Among Patients With Early‐Onset Metastatic Colorectal Cancer

BACKGROUND AND OBJECTIVES: The incidence of early-onset colorectal cancer (eoCRC) is rising, yet optimal management in the metastatic setting remains unclear. We characterized and compared treatment patterns among patients with early-onset and later-onset (loCRC) metastatic CRC, and evaluated outcomes by treatment regimen among patients with eoCRC. METHODS: We performed a retrospective analysis of patients diagnosed with stage IV CRC between 2004 and 2022. Patients were stratified by age (eoCRC, < 50 years; loCRC, 50-59.9 [reference], 60-69.9, and ≥ 70). Utilization of systemic chemotherapy (CT), primary resection (PR), immunotherapy (IO), and metastasis resection (MR) were compared across age groups. Among patients with eoCRC, overall survival was compared by treatment regimen. RESULTS: Among 259,435 patients with stage IV CRC, 15.6% were classified as eoCRC. Compared with patients with loCRC, those with eoCRC were more likely to undergo multimodal treatment regimens including CT/PR, CT/PR/MR, and CT/PR/IO (p < 0.05 for all). Among patients with eoCRC, CT/PR (adjusted HR 0.49, 95% CI 0.47-0.51), CT/PR/MR (HR 0.36, 95% CI 0.34-0.38), and CT/PR/IO (HR 0.52, 95% CI 0.49-0.55) were associated with the greatest survival benefit, versus CT alone. CONCLUSIONS: Patients with metastatic eoCRC more frequently received aggressive, multimodal therapy, which was associated with improved survival.