Impact of genetic alterations on long-term outcomes in resectable intrahepatic cholangiocarcinoma: meta-analysis

Abstract

Background: Intrahepatic cholangiocarcinoma is a public health threat because of its aggressiveness. Its genetic background differs from other biliary cancers. The aim of this study was to investigate the impact of genetic alterations on long-term outcomes. Methods: PubMed, MEDLINE, Scopus, and Cochrane Library databases were systematically searched for studies assessing long-term outcomes after resection of intrahepatic cholangiocarcinoma according to genetic mutational profiling until 31 May 2022. The main outcome was the impact of genetic alterations on long-term outcomes in these patients. HR (95% c.i.) was used for effect size. Publication bias was investigated. Results: A total of 24 retrospective studies were included. KRAS, IDH1/2, and TP53 were identified as the only three genes whose mutation correlated with survival (HR: 2.476, 95% c.i. 1.67-3.671, P < 0.01 for KRAS; HR: 0.624, 95% c.i. 0.450-0.867, P < 0.01 for IDH1/2; and HR: 2.771, 95% c.i. 2.034-3.775, P < 0.01 for TP53). The prevalence of KRAS and IDH1/2 mutations differed between western and eastern studies (P < 0.001 for both genes). Conclusion: Determining the overall prevalence of the most common actionable and undruggable mutations may help to expand target therapy indications in the adjuvant setting. Inconsistent results have been found for some infrequent gene alterations; their rare involvement could potentially bias their prognostic meaning.