Prognostic factors for progression-free and overall survival in advanced biliary tract cancer.
BACKGROUND
Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease.


METHODS
Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset.


RESULTS
A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)].


CONCLUSIONS
These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.
UCL Cancer Institute, UCL, London j.bridgewater@ucl.ac.uk.
J
J
Bridgewater
UCL and CRUK Clinical Trials Centre, UCL, London.
A
A
Lopes
Department of Oncology, Imperial Healthcare, London, UK.
H
H
Wasan
Department of Cancer Medicine, Institute Gustave Roussy, Paris, France.
D
D
Malka
Department of Oncology, Vejle Hospital, Vejle, Denmark.
L
L
Jensen
Division of Hepatobiliary and Pancreatic Oncology, National Cancer Centre Hospital, Tokyo, Japan.
T
T
Okusaka
Department of Oncology, Princess Margaret Cancer Centre, Toronto, Canada.
J
J
Knox
Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
D
D
Wagner
Department of Medicine, Royal Marsden Hospital, Sutton, UK.
D
D
Cunningham
Department of Oncology, Nepean Cancer Centre, Sydney.
J
J
Shannon
Department of Oncology, Prince of Wales Hospital, Sydney, Australia.
D
D
Goldstein
Department of Internal Medicine, Johannes Gutenberg-University of Mainz, Mainz, Germany.
M
M
Moehler
Department of Oncology, The Ohio State University, Columbus, USA.
T
T
Bekaii-Saab
Institute of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK.
M G
MG
McNamara
Institute of Cancer Sciences, The University of Manchester and The Christie NHS Foundation Trust, Manchester, UK.
J W
JW
Valle
D001650:Bile Duct Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018281:Cholangiocarcinoma / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D018572:Disease-Free Survival; D006801:Humans; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D016896:Treatment Outcome
ABC-02; advanced disease; biliary tract cancer; cisplatin and gemcitabine; performance status; prognostic model