Guidelines Summary
Guidelines Contributor: Elwyn C Cabebe, MD Physician Partner, Valley Medical Oncology Consultants; Medical Director of Oncology, Clinical Liason Physician, Cancer Care Committee, Good Samaritan Hospital
Diagnosis
The National Comprehensive Cancer Network (NCCN) recommends the following intrahepatic cholangiocarcinoma workup in patients with an isolated intrahepatic mass that has imaging characteristics consistent with malignancy but not consistent with hepatocellular carcinoma [40] :
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History and physical examination
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Multiphasic abdominal/pelvic computed tomography (CT)/magnetic resonance imaging (MRI) with intravenous contrast
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Chest CT with or without contrast
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Consider baseline carcinoembryonic antigen (CEA) and CA 19-9 testing
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Liver function tests (LFTs)
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Surgical consultation
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Esophagogastroduodenoscopy (EGD) and colonoscopy (to assess for T3 disease and rule out endobiliary metastasis from colorectal cancer mimicking intrahepatic cholangiocarcinoma [47] )
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Consider viral hepatitis serologies
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Consider biopsy
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Consider alpha fetoprotein (AFP) testing
For the workup of extrahepatic cholangiocarcinoma, in patients who present with pain, jaundice, abnormal LFTs, and obstruction or abnormality on imaging, the NCCN recommends the following workup [40] :
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History and physical examination
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Multiphasic abdominal/pelvic CT/MRI (to assess for vascular invasion) with IV contrast
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Chest CT with or without contrast
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Cholangiography
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Consider baseline CEA and CA 19-9
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LFTs
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Consider endoscopic ultrasound (EUS) after surgical consultation
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Consider serum IgG4 to rule out autoimmune cholangitis
Guidelines from the American Society for Gastrointestinal Endoscopy (ASGE) recommend magnetic resonance cholangiography (MRCP) to assess for resectability if a CT scan suggests cholangiocarcinoma. ERCP is recommended to obtain tissue or facilitate further evaluation of indeterminate strictures. [48]
Staging
Cholangiocarcinoma cancer staging follows the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control/ (AJCC/UICC) and is staged separately for intrahepatic, perihilar, and distal bile duct tumors. [27]
TNM groupings by stage are as follows for each group: [27]
Table. 1 (Open Table in a new window)
Intrahepatic bile duct tumor |
|||
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
IA |
T1a |
N0 |
M0 |
IB |
T1b |
N0 |
M0 |
II |
T2 |
N0 |
M0 |
IIIA |
T3 |
N0 |
M0 |
IIIB |
T4 |
N0 |
M0 |
|
Any T |
N1 |
M0 |
IV |
Any T |
Any N |
M1 |
Table. 2 (Open Table in a new window)
Perihilar bile duct tumor |
|||
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
I |
T1 |
N0 |
M0 |
II |
T2a-b |
N0 |
M0 |
IIIA |
T3 |
N0 |
M0 |
IIIB |
T4 |
N0 |
M0 |
IIIC |
Any T |
N1 |
M0 |
IVA |
T4 |
N2 |
M0 |
IVB |
Any T |
Any N |
M1 |
Table. 3 (Open Table in a new window)
Distal bile duct tumor |
|||
Stage |
T |
N |
M |
0 |
Tis |
N0 |
M0 |
I |
T1 |
N0 |
M0 |
IIA |
T1 |
N1 |
M0 |
|
T2 |
N0 |
M0 |
IIB |
T2 |
N1 |
M0 |
|
T3 |
N0 |
M0 |
|
T3 |
N1 |
M0 |
IIIA |
T1-3 |
N2 |
M0 |
IIIB |
T4 |
N0-2 |
M0 |
IV |
Any T |
Any N |
M1 |
Treatment
The NCCN and ESMO guidelines concur that the only potentially curative treatment for cholangiocarcinoma is complete surgical resection with negative margins. However, few patients are diagnosed with early-stage resectable tumors. [40, 49]
With cholangiocarcinomas that are resected with negative margins and negative regional nodes, the NCCN recommends observation or systemic therapy (with gemcitabine as the preferred agent) for both intrahepatic and extrahepatic cholangiocarcinomas; for extrahepatic cholangiocarcinomas, fluoropyrimidine chemoradiation is also an option.
For intrahepatic and extrahepatic cholangiocarcinomas resected with microscopic margins or positive regional nodes, options include the following:
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Systemic therapy
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Fluoropyrimidine-based chemoradiation
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Fluoropyrimidine- or gemcitabine-based chemotherapy followed by fluoropyrimidine-based chemoradiation
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Fluoropyrimidine-based chemoradiation followed by fluoropyrimidine- or gemcitabine-based chemotherapy
For intrahepatic or extrahepatic resections with residual local disease, or unresectable disease, NCCN suggestions include systemic therapy, external beam radiation therapy (EBRT) with concurrent fluoropyrimidine, or best supportive care. The choice of care may be guided by the extent and/or location of disease and institutional capabilities. [40]
For metastatic disease, options for intrahepatic cholangiocarcinomas include systemic therapy, consideration of locoregional therapy (eg, EBRT, arterially directed therapies), or best supportive care. For extrahepatic cholangiocarcinomas, options are systemic therapy or best supportive care. [40]
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Bismuth classification for perihilar cholangiocarcinoma. Shaded areas represent tumor location.
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Tight stricture of a common hepatic duct in a patient presenting with jaundice. Cytologic studies confirmed cholangiocarcinoma.
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Three-dimensional treatment planning uses CT scan slices to reconstruct the patient as a volume. Shown here is the display for planning external-beam radiotherapy to the cholangiocarcinoma (green structure). A biliary catheter (red tube) runs through the tumor volume and was used to deliver brachytherapy, which was given in addition to external-beam radiotherapy. Such technology has assisted greatly in the delivery of high doses to the tumor, while sparing vital normal structures, such as the kidney and spinal cord.