Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
Authors: Bangolo Ayrton , Nagesh Vignesh K. , Tran Hadrian Hoang-Vu , Sens Brooke , Elias Daniel , Amoozgar Behzad , Tomasino Chase , Kianifar Aguilar Izage , Mansour Charlene , Gagen Elizabeth , Zhang Lili , Gill Sarvarinder , Jebara Nisrene , Madigan Emma , Candela Christin , Amin Dohaa , Giunta Peter , Singh Shubhangi , Siddiqui Aman , Auda Auda , Peej Paul , Fong Timophyll Y. H. , Weissman Simcha , Lihau Printhia Matshi , Bukasa-Kakamba John 
Published: January 2025

Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.