Intrahepatic Cholangiocarcinoma: Epidemiological Trends, Risk Factors, Diagnostic Challenges, and Advances in Personalized Therapy-A Comprehensive Review.

Intrahepatic cholangiocarcinoma (iCCA) ranks as the second most common primary liver cancer, compared to about 20% of cases. Its global incidence has climbed over the past four decades, yet early detection remains indefinable due to its asymptomatic nature. Five-year survival rate of approximately is under 10%. Surgical resection is the solitary therapeutic option; only 20%-30% of patients are eligible, with high postsurgical resection relapse rates. Adjuvant capecitabine has become standard postoperative care following the BILCAP trial outcome. Intended for nonresectable cases, systemic therapy with gemcitabine + cisplatin serves as first-line therapy (median OS, 11.7 months). Emerging locoregional approaches, radioembolization, hepatic artery infusion (HAI), and ablation provide intrahepatic disease control. This review charts iCCA's rising incidence and mortality, predisposing factors, diagnostic obstacles, and current and future therapeutic strategies. Improved outcomes depend on translating current research into routine biomarker testing and targeted therapies for iCCA. Future directions hinge on wider liquid biopsy adoption, especially ctDNA testing to enable earlier iCCA detection, real-time monitoring, and faster therapy adjustments against emerging resistance. Routine molecular profiling identifies FGFR fusions and IDH1 mutations to guide targeted iCCA therapies; steady funding and tumor board integration remain essential for broader access.