Prognostic Significance of Lymph Node Ratio in Intrahepatic and Extrahepatic Cholangiocarcinomas

Background/Objectives. Lymph Node Ratio (LNR) is increasingly recognized as an important prognostic factor in various cancer types, with the potential to enhance patient stratification for intrahepatic (ICC) and extrahepatic (ECC) cholangiocarcinoma. The study aimed to assess the impact of LNR on survival in surgically resected patients with ICC and ECC. Methods. This was a retrospective analysis of National Cancer Database (2004-2020) included ICC and ECC (excluding distal bile duct) patients who underwent primary site resection with adequate lymphadenectomy (≥4 LNs excised). Exclusions comprised age < 18 years, distant metastasis, or incomplete key data. LNR was calculated as the ratio of positive LNs to total examined LNs. Survival probabilities were estimated using Kaplan-Meier analysis and Cox regression. Results. The inclusion criteria were met by 954 patients with ICC and 1607 patients with ECC. In patients with ICC, the median OS time was 62.7 months in LNR0 group, 40.8 months in LNR < 30%, and 25.2 months in LNR ≥ 30% (p < 0.001). In ICC, 3-year OS was 69.3%, 54.6%, and 34% for LNR 0, LNR < 30%, and LNR ≥ 30%, respectively (p < 0.05). When adjusted for age, sex, Charlson-Deyo score, histology, surgical margins, chemo- and radiotherapy using Cox regression, LNR < 30% and LNR ≥ 30% were associated with worse OS in patients with ICC (HR 2.1 (95% CI 1.6-2.7) and HR 2.94 (95% CI 2.3-3.8)) and ECC (HR 2.1 (95% CI 1.8-2.5) and HR 3 (95% CI 2.4-3.7)). Conclusions. It is well-known that LN-negative patients have significantly better survival than LN-positive patients with ICC and ECC. This study strongly demonstrates that survival prognosis can be further stratified based on LNR for ICC and ECC patients and that it is not simply a binary factor.