Abstract
BACKGROUND: The incidence of young-onset cholangiocarcinoma (YOCC) is rising, yet the survival outcomes and metastatic patterns of metastatic YOCC (mYOCC) compared to metastatic average-onset cholangiocarcinoma (mAOCC) remain unclear. This study evaluates differences in survival outcomes, metastatic patterns, and associated prognostic factors between mYOCC and mAOCC. METHODS: A retrospective cohort study was conducted using the SEER database (2018-2021), including patients aged ≥18 years with metastatic cholangiocarcinoma (mCC). Patients were stratified into mYOCC (<50 years) and mAOCC (≥50 years). Clinical characteristics, metastatic sites, and treatment modalities were analyzed. Kaplan-Meier and Cox proportional hazards models were used to assess overall survival (OS) and cancer-specific survival (CSS). RESULTS: Of 1,601 patients with mCC, 9.99% had mYOCC. mYOCC patients were younger (median age 44 vs. 66 years, p<0.001) and more frequently presented with bone (27.50% vs. 19.36%, p=0.015) and lung metastases (36.25% vs. 27.48%, p=0.021). They also had a higher prevalence of multiple-site metastases, including bone-liver-lung combinations (7.50% vs. 3.33%, p=0.008). Median survival was 12 months for mYOCC versus 9 months for mAOCC. mYOCC patients had a lower risk of mortality (aHR=0.74, 95% CI: 0.60-0.93, p=0.01). Treatment modalities, including chemotherapy and surgery, significantly improved survival, regardless of age at diagnosis. CONCLUSION: mYOCC demonstrates distinct metastatic patterns, including higher frequencies of bone and lung metastases, and is associated with better survival outcomes compared to mAOCC. These findings highlight the need for age-specific diagnostic and therapeutic approaches to improve outcomes for mYOCC patients. Further research is needed to understand the biological mechanisms underlying these differences and address disparities in survival outcomes.