Lymph node dissection in intrahepatic cholangiocarcinoma: Cutting through heterogeneity to reveal the survival signal of an adequate dissection

BACKGROUND: The therapeutic benefit of lymph node dissection in intrahepatic cholangiocarcinoma remains controversial, obscured by significant heterogeneity and confounding in the existing literature. We performed an updated meta-analysis to determine the impact of lymph node dissection on overall survival and to investigate the sources of this inconsistency. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched multiple databases through July 2025 for studies comparing lymph node dissection versus no lymph node dissection in patients undergoing resection for intrahepatic cholangiocarcinoma. Pooled hazard ratios for overall survival were calculated using a random-effects model. Prespecified analyses stratified studies by author-defined lymph node dissection adequacy (where individual studies established their own threshold for what constituted an adequate lymph node harvest) and a standardized threshold of ≥6 retrieved lymph nodes. Meta-regression assessed the influence of propensity-score matching and country of origin. RESULTS: = 86%). Meta-regression revealed that both the use of propensity-score matching and country of origin were significant effect modifiers (P = .0002). Studies using propensity-score matching showed a significant survival benefit for lymph node dissection (hazard ratio = 0.58, 95% confidence interval = 0.44-0.77). Although author-defined adequate lymph node dissection showed a nonsignificant trend toward benefit (hazard ratio = 0.78, 95% confidence interval = 0.56-1.07, P = .09), a post hoc analysis using a standardized threshold demonstrated that retrieval of ≥6 lymph nodes was associated with a significant survival advantage (hazard ratio = 0.76, 95% confidence interval = 0.66-0.89, P = .02). CONCLUSION: The apparent lack of a universal survival benefit for lymph node dissection in intrahepatic cholangiocarcinoma is a consequence of methodologic heterogeneity and confounding. When these biases are mitigated, a significant therapeutic signal emerges. The retrieval of ≥6 lymph nodes is associated with a clear survival advantage, reinforcing that adequate lymphadenectomy is critical not only for accurate staging but also for its potential therapeutic benefit. This finding mandates standardization of the lymph node dissection template in future prospective studies.