Recurrence Patterns and Disease-Free Survival after Resection of Intrahepatic Cholangiocarcinoma: Preoperative and Postoperative Prognostic Models.
Liver resection is the most effective treatment for intrahepatic cholangiocarcinoma. Recurrent disease is frequent; however, recurrence patterns are ill-defined and prognostic models are lacking.



A primary cohort of 189 patients who underwent resection for intrahepatic cholangiocarcinoma was used for recurrence patterns analysis within and after 24 months. Based on independent factors for disease-free survival identified in Cox regression analysis, preoperative and postoperative models were developed using a recursive partitioning method. Models were externally validated using a multicenter cohort of 522 resected patients (Association Française de Chirurgie intrahepatic cholangiocarcinoma study group).



Recurrence within 24 months most often involved the liver (82.7%), and most recurrences after 24 months were strictly extrahepatic (61.1%). In multivariable analysis of the primary cohort, independent preoperative factors for disease-free survival were tumor size and multifocality (based on imaging); tumor size, multifocality, vascular invasion, and lymph node metastases (based on pathology) were independent postoperative factors. The preoperative model allowed patient classification into low-risk and high-risk groups for recurrence. In the validation cohort (n = 522), high-risk patients had a greater likelihood of recurrence (hazard ratio = 2.17; 95% CI, 1.74-2.72; p < 0.001). The postoperative model included tumor size, vascular invasion, and positive nodal disease on pathology and classified patients in low-, intermediate-, and high-risk groups in the primary cohort. As compared with low-risk patients in the validation cohort, intermediate- and high-risk patients were more likely to experience recurrence (hazard ratio = 1.9; 95% CI, 1.41-2.47; p < 0.001 and hazard ratio = 2.99; 95% CI, 2.08-4.31; p < 0.001, respectively).



Recurrence patterns are time dependent. Both models as developed and validated in this study classified patients in distinct recurrence risk groups, which can guide treatment recommendations.
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, AP-HP, Créteil, France.
Alexandre
A
Doussot
Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY.
Mithat
M
Gonen
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Jimme K
JK
Wiggers
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Bas
B
Groot-Koerkamp
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Ronald P
RP
DeMatteo
Department of Digestive Pathology, Institut Mutualiste Montsouris, Paris Descartes University, Paris, France.
David
D
Fuks
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Peter J
PJ
Allen
Department of Hepatobiliary Surgery, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, AP-HP, Université Paris 7, Clichy, France.
Olivier
O
Farges
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
T Peter
TP
Kingham
Department of Surgery, CHU Amiens, Amiens, France.
Jean Marc
JM
Regimbeau
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Michael I
MI
D'Angelica
Department of Hepatobiliary Surgery and Liver Transplantation, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris, AP-HP, Créteil, France.
Daniel
D
Azoulay
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: jarnagiw@mskcc.org.
William R
WR
Jarnagin
D000368:Aged; D001650:Bile Duct Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018281:Cholangiocarcinoma / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D006498:Hepatectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome