Cholangiocarcinoma Treatment & Management

Updated: Aug 30, 2018
  • Author: Peter E Darwin, MD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment

Approach Considerations

Complete surgical resection is the only therapy to afford a chance of cure for cholangiocarcinoma. Unfortunately, many patients present with unresectable disease. Additional treatment measures in cholangiocarcinoma may include the following [8] :

  • Stenting
  • Photodynamic therapy (PDT)
  • Radiation therapy
  • Chemotherapy

For palliative treatment, celiac-plexus block via regional injection of alcohol or other sclerosing agent can relieve pain in the mid back from retroperitoneal tumor growth. In addition, other endoscopic forms of palliation, such as brachytherapy and radiofrequency ablation, have been used. [24, 25]

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Stent Placement

Stents can be placed via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC) to relieve biliary obstruction. Stenting may relieve pruritus and improve quality of life.

Stents usually are used if the tumor is unresectable or if the patient is not a surgical candidate. Debate exists about whether preoperative stenting is warranted, but most surgeons believe that preoperative biliary decompression does not alter the outcome of surgery.

Either plastic or metal stents may be used. Plastic stents usually occlude in 3 months and require replacement. Metal stents are more expensive but expand to a larger diameter and tend to stay patent longer. Adequate biliary drainage can be achieved in a high percentage of cases. A study by Kida et al found that covered biliary self-expandable metal stents could be safely removed when they become occluded and that patency rates were similar for reintervention and initial stent placement. [26]

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Photodynamic Therapy

Photodynamic therapy (PDT) is an experimental local cancer therapy already in use for other gastrointestinal malignancies. [27, 28]  PDT is a two-step process: the first step is intravenous (IV) administration of a photosensitizer; the second step is activation by light illumination at an appropriate wavelength. [27, 28]

PDT is effective in restoring biliary drainage and improving quality of life in patients with nonresectable disseminated cholangiocarcinomas. Survival times may be longer than those reported previously. A prospective, multicenter study showed a significant survival benefit in the PDT treatment group. [27]  An additional multicenter study is being planned.

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Radiation Therapy

Adjuvant and preoperative radiation therapy has been used to reduce tumors in an effort to make them resectable. This therapy has been performed with and without concurrent chemotherapy as a radiation sensitizer.

The value of adjuvant radiotherapy has been to improve local control, with variable effect on overall survival after complete resection. Several series have shown an increase in median survival duration with postoperative radiation, from 8 months with surgery alone to more than 19 months.

Special radiation techniques have been used, such as intraluminal brachytherapy and external-beam therapy during surgery (ie, intraoperative radiotherapy [IORT]). See the image below for treatment planning technique.

Three-dimensional treatment planning uses CT scan 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.

In patients with medially inoperable or unresectable tumors, primary radiotherapy, with or without chemotherapy, has provided a survival advantage and significant palliation over stent placement or bypass surgery alone.

In a study of 1636 patients with unresectable localized intrahepatic cholangiocarcinoma, the addition of radiation to chemotherapy was associated with an improvement in overall survival. Two-year overall survival was 20% for the chemotherapy-alone cohort versus 26% for the chemoradiation therapy group. [29]

Radioembolization with yttrium-90 has been shown to be safe and effective in patients with unresectable/recurrent intrahepatic cholangiocarcinoma. Mosconi et al reported significantly longer survival in patients who received radioembolization as initial therapy, compared with patients in whom radioembolization was preceded by other treatments, including surgery (52 vs 16 months, P=0.009). [30]

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Chemotherapy

Most often, chemotherapy is given in low doses to act as a radiation sensitizer during a 4- to 5-week course of external-beam radiotherapy. Primary chemotherapy has been evaluated as well, including gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma. [31, 32]  However, chemotherapy agents used without radiotherapy or surgery do not appear to provide any local control or meaningful survival benefit.

The most used agent has been 5-fluorouracil, which has a partial response rate of about 12%. Gemcitabine has a similar response rate. Although fluoropyrimidines and doxorubicin have been reported to have response rates as high as 30-40%, partial responses lasting from weeks to months have been observed in only 10-35% of trials. [31, 32] >

For patients with intrahepatic cholangiocarcinomas who have no residual local disease after resection, the National Comprehensive Cancer Network (NCCN) suggests observation or adjuvant fluoropyrimidine- or gemcitabine-based chemotherapy. For lesions that are resected with microscopic margins or positive regional nodes, the NCCN recommends fluoropyrimidine chemoradiation or fluoropyrimidine- or gemcitabine-based chemotherapy. No data support aggressive surveillance, but imaging every 6 months for 2 years may be considered, if clinically indicated. [33]

For intrahepatic cholangiocarcinoma with residual local disease after resection, the NCCN's only category 1 recommendation is gemcitabine/cisplatin combination therapy. Locoregional care is a category 2B recommendation, with fluoropyrimidine-based or other gemcitabine-based chemotherapy or best supportive care as other alternatives. [33]

For unresectable extrahepatic cholangiocarcinoma, the NCCN recommends gemcitabine/cisplatin combination therapy (category 1). Alternatives are fluoropyrimidine-based or other gemcitabine-based chemotherapy regimen or fluoropyrimidine chemoradiation. The NCCN also recommends gemcitabine/cisplatin combination therapy as a category 1 option for metastatic extrahepatic cholangiocarcinoma, with fluoropyrimidine-based or other gemcitabine-based chemotherapy regimens as alternatives. [33]

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Surgical Care

Complete surgical resection is the only therapy to afford a chance of cure. Unfortunately, only 10% of patients present with early-stage disease and are candidates for curative resection. Intrahepatic and Klatskin tumors [7] require liver resection, which may not be an option for older patients with comorbid conditions. In one report, 15% of patients with proximal lesions were candidates for complete resections, with higher rates in patients with mid-ductal tumors (33%) or distal tumors (56%). The survival rate for patients with proximal tumors can be 40% if negative margins are obtained.

Orthotopic liver transplantation is considered for some patients with proximal tumors who are not candidates for resection because of the extent of tumor spread in the liver. The largest series reports a 53% 5-year survival rate and a 38% complete pathologic response rate with preoperative radiation therapy and chemotherapy. Liver transplantation may have a survival benefit over palliative treatments, especially for patients with tumors in the initial stages. One study has demonstrated a 5-year survival rate greater than 80% in select patients. [34]

Distal tumors are resected via Whipple procedure; periampullary region tumors have a uniformly better prognosis, with a long-term survival rate of 30-40%.

Patterns of treatment failure after curative surgery show disappointingly high rates of tumor bed and regional nodal recurrence. This finding may be due in part to the narrow pathologic margins; however, the regional node failure rate is approximately 50%, and the distal metastases rate is 30-40%. Failure rates correlate with TNM stage. Adjuvant transcatheter arterial chemoembolization for intrahepatic cholangiocarcinoma has been used post attempted curative surgery, with better survival in patients with early recurrence. [35]

Palliative procedures are required if internal stenting cannot be accomplished and/or external stenting is not desirable or cannot be obtained. Surgical bypass, particularly for tumors in the common bile duct, should be performed in such cases.

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Consultations

Gastroenterologists, interventional radiologists, and transplant/biliary surgeons play a key role in diagnosis and management. Radiation oncology and medical oncology specialists are part of the multidisciplinary team taking part in the treatment of both patients with curatively resected tumors and those with unresectable tumors. Radiation oncologists have taken a more significant role in therapy for cholangiocarcinomas since the early 1980s.

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