TY - JOUR
T1 - Predicting recurrence in patients with node-negative perihilar cholangiocarcinoma after an R0 resection
AU - Perihilar Cholangiocarcinoma Study Group
AU - Wei, Tao
AU - Zhang, Jian
AU - Chatzipanagiotou, Odysseas P.
AU - Guo, Shouliang
AU - Guglielmi, Alfredo
AU - Marques, Hugo P.
AU - Aucejo, Federico
AU - Maithel, Shishir K.
AU - Pulitano, Carlo
AU - Poultsides, George A.
AU - Zhang, Xu Feng
AU - Groot Koerkamp, Bas
AU - Itaru, Endo
AU - Liang, Tingbo
AU - Pawlik, Timothy M.
N1 - Publisher Copyright:
© 2026 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. http://creativecommons.org/licenses/by-nc-nd/4.0/
PY - 2026/5
Y1 - 2026/5
N2 - Background: Resection margin status and lymph node involvement are well-established predictors of recurrence following resection of perihilar cholangiocarcinoma (pCCA). However, even patients with favorable pathology including negative surgical margins (R0) and node-negative disease (N0) may experience recurrence. We sought to develop a clinically relevant tool to risk stratify patients relative to tumor recurrence following an R0N0 resection of pCCA. Methods: pCCA patients undergoing curative-intent resection with R0 and N0 tumor were identified from an international multi-institutional database. A pathology-based risk score was developed to predict recurrence-free survival (RFS). In addition, genomic profiling was performed in a subset of patients to evaluate the prognostic relevance of genetic alterations. Results: Among 298 patients with resected R0N0 pCCA, 131 (44.0%) developed disease recurrence. Multivariable analysis identified advanced AJCC T category (T2b or T3/T4), perineural invasion, and poor tumor differentiation as independent predictors of inferior RFS. Based on these factors, a three-variable pathology-based risk score stratified patients into low-, intermediate-, and high-risk groups with corresponding 3-year RFS of 85%, 31%, and 27%, respectively. Both intermediate- and high-risk patients had worse RFS versus low-risk patients (high-risk vs. low-risk: median RFS, 15.0 vs. 92.9 months; intermediate-risk vs. low-risk: median RFS, 23.0 vs. 92.9 months; both p < 0.001). KRAS mutations occurred in 29% of profiled patients, which was associated with reduced RFS (mutant vs. wild-type KRAS: median RFS, 11.0 vs. 24.0 months, p = 0.011). Conclusions: Recurrence risk among patients with R0N0 pCCA was heterogeneous. The proposed risk score stratified patients into markedly different risk categories relative to recurrence, which may help guide utilization of adjuvant therapy as well as surveillance in the postoperative setting.
AB - Background: Resection margin status and lymph node involvement are well-established predictors of recurrence following resection of perihilar cholangiocarcinoma (pCCA). However, even patients with favorable pathology including negative surgical margins (R0) and node-negative disease (N0) may experience recurrence. We sought to develop a clinically relevant tool to risk stratify patients relative to tumor recurrence following an R0N0 resection of pCCA. Methods: pCCA patients undergoing curative-intent resection with R0 and N0 tumor were identified from an international multi-institutional database. A pathology-based risk score was developed to predict recurrence-free survival (RFS). In addition, genomic profiling was performed in a subset of patients to evaluate the prognostic relevance of genetic alterations. Results: Among 298 patients with resected R0N0 pCCA, 131 (44.0%) developed disease recurrence. Multivariable analysis identified advanced AJCC T category (T2b or T3/T4), perineural invasion, and poor tumor differentiation as independent predictors of inferior RFS. Based on these factors, a three-variable pathology-based risk score stratified patients into low-, intermediate-, and high-risk groups with corresponding 3-year RFS of 85%, 31%, and 27%, respectively. Both intermediate- and high-risk patients had worse RFS versus low-risk patients (high-risk vs. low-risk: median RFS, 15.0 vs. 92.9 months; intermediate-risk vs. low-risk: median RFS, 23.0 vs. 92.9 months; both p < 0.001). KRAS mutations occurred in 29% of profiled patients, which was associated with reduced RFS (mutant vs. wild-type KRAS: median RFS, 11.0 vs. 24.0 months, p = 0.011). Conclusions: Recurrence risk among patients with R0N0 pCCA was heterogeneous. The proposed risk score stratified patients into markedly different risk categories relative to recurrence, which may help guide utilization of adjuvant therapy as well as surveillance in the postoperative setting.
KW - KRAS mutation
KW - Node-negative disease
KW - Perihilar cholangiocarcinoma
KW - R0 resection
KW - Recurrence
UR - https://www.scopus.com/pages/publications/105034144526
U2 - 10.1016/j.ejso.2026.111751
DO - 10.1016/j.ejso.2026.111751
M3 - 文章
C2 - 41850029
AN - SCOPUS:105034144526
SN - 0748-7983
VL - 52
JO - European Journal of Surgical Oncology
JF - European Journal of Surgical Oncology
IS - 5
M1 - 111751
ER -