Cholangiocarcinoma Treatment & Management
- Author: Peter E Darwin, MD; Chief Editor: N Joseph Espat, MD, MS, FACS more...
Treatment of cholangiocarcinoma may include the following:
Photodynamic therapy (PDT)
For palliative treatment, celiac-plexus block via regional injection of alcohol or other sclerosing agent can relieve pain in the mid back that is associated with retroperitoneal tumor growth. In addition, other endoscopic forms of palliation, such as brachytherapy and radiofrequency ablation, have been used.[16, 17]
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 at the time of stent occlusion and that patency rates were similar for reintervention and initial stent placement.
PDT is an experimental local cancer therapy already in use for other gastrointestinal malignancies.[19, 20] 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.[19, 20]
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. An additional multicenter study is being planned.
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.
Primary radiotherapy without surgery, with or without chemotherapy, has provided a survival advantage and significant palliation over stent placement or bypass surgery alone in patients with medially inoperable or unresectable tumors.
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.[21, 22] However, chemotherapy agents used without radiotherapy or surgery do not appear to provide any local control or meaningful survival benefit.
The most used agent is 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.[21, 22]
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 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.
The National Comprehensive Cancer Network suggests reresection, ablation, or chemotherapy for intrahepatic cholangiocarcinomas that are resected with microscopic margins or residual local disease. Those with no residual local disease after resection can be followed with imaging periodically.
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.
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%. Failures are correlated 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.
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.
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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