Survival Analysis of Metastatic Young-Onset vs. Average-Onset Cholangiocarcinoma: A Population-Based Study

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.

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).

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.

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.