Biliary Tract Cancer Treatment Protocols

Updated: Jun 16, 2021
  • Author: Jeffrey B VanDeusen, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Treatment Protocols

Treatment protocols for biliary tract cancer are provided below, including the following [1, 2] :

  • Surgery
  • Adjuvant therapies
  • Systemic therapies
  • Single-agent regimens

Surgical resection

See the list below:

  • Surgery is the only curative modality for biliary tract cancers; surgical resectability of disease should be established by care teams who are experts in the field

  • Criteria for resectability include absence of all of the following: retropancreatic and paraceliac nodal metastases or distant liver metastases, invasion of the portal vein or main hepatic artery (although some centers can offer vascular reconstruction), extrahepatic adjacent organ invasion, and disseminated disease

  • Surgical resection generally includes cholecystectomy, en bloc hepatic resection, and lymphadenectomy with or without bile duct excision, depending on the location of the tumor [3]

  • If cancer is found incidentally at the time of surgery for other reasons and resectability is not clearly established or if the surgeon is not trained in the operation, then delayed open laparotomy is appropriate, as there is not a survival deficit compared to immediate resection [4]

Neoadjuvant therapy

Neoadjuvant chemoradiotherapy is not currently a standard option for patients with biliary tract cancer. In a small selected case series, 9 of 91 patients presenting with more advanced disease received chemoradiotherapy and all achieved an R0 resection [5] ; however, a later study investigating chemoradiotherapy with 5-FU did not show a survival benefit. [5]

In a retrospective analysis by Kobayashi et al, chemoradiation therapy with three cycles of full-dose gemcitabine plus 50-60 Gy radiation improved recurrence-free survival (P = 0.0263) and overall survival  (P = 0.00187). In 27 patients who received neoadjuvant chemoradiation therapy, 3-year recurrence-free was 78%, versus 58% in 79 patients treated without neoadjuvant therapy. [6]

For patients with early stage, unresectable hilar cholangiocarcinoma or cholangiocarcinoma arising in the setting of primary sclerosing cholangitis, high-dose neoadjuvant radiotherapy with chemosensitization, followed by liver transplantation, achieves excellent results. [7] The Mayo Clinic protocol is as follows:

  • External beam radiation therapy plus continuous 5-FU for 3 weeks, then 
  • Brachytherapy for 2 weeks,  then
  • Capecitabine until transplantation (held perioperatively during staging),  then
  • Abdominal exploration for staging,  then
  • Liver transplantation

Adjuvant therapy following curative-intent resection

Stage IB-III (T1-3, N0-1, M0):

  • Spanish Society of Medical Oncology (SEOM) guidelines recommend that all patients who have undergone curative resection of biliary tract cancer receive adjuvant therapy with capecitabine for 6 months. [1]

  • National Comprehensive Cancer Network (NCCN) guidelines note that only limited clinical trial data are available to define a standard regimen or definitive benefit, and encourage clinical trial participation, but offer the options of fluoropyrimidine- or gemcitabine-based chemotherapy followed by fluoropyrimidine-based chemoradiation, or fluoropyrimidine-based chemoradiation, which may be followed by fluoropyrimidine- or gemcitabine-based chemotherapy. [8]

  • Recommendations for radiation therapy in the adjuvant setting stem from high rates of local failure following surgery, and a retrospective analysis of patients receiving adjuvant radiotherapy shows an initial survival benefit; however, a longer-term follow-up series suggests that this benefit may be lost after more than 5 years. [9]

Adjuvant chemoradiotherapy regimens for stage IB-III:

  • 5-FU 225 mg/m2 IV daily during radiation [10]  or

  • 5-FU 500 mg/m2 IV bolus on days 1-3 and days 29-31 during radiation [8]  or

  • Capecitabine 825 mg/m2 PO twice daily during radiation [11] ; following radiation, consider an additional 4 mo of therapy [12] or

  • Capecitabine 1000 mg/m2 PO twice daily for 14 of every 21d [13] or

  • Capecitabine 800-900 mg/m2 PO BID on days of radiation [8]

  • For those with aggressive or high-risk disease (positive margins) or multiple positive lymph nodes, consider switching to a gemcitabine-based regimen (see Systemic therapy, below).

Systemic therapy for nonresectable or metastatic disease

Selected stage III-IV (T3-4, Any N, M0-1):

Standard-of-care front-line chemotherapy for patients with good performance status (ECOG score ≤2) [14] :

  • Cisplatin 25 mg/m2 IV on days 1 and 8 plus gemcitabine 1000 mg/m2 IV on days 1 and 8; then every 21d for up to 24wk or until disease progression

Other acceptable regimens for good performance status patients (gemcitabine regimens favored) [15] :

  • Gemcitabine 1000 mg/m2 IV on day 1 plus oxaliplatin 100 mg/m2 IV on day 2; then every 14d until progression or toxicity [15] or

  • Gemcitabine 1000 mg/m2 IV on days 1 and 8 plus  capecitabine 650 mg/m2 PO on days 1-14; then every 21d until progression or toxicity [16] or

  • Capecitabine 1000 mg/m2 PO twice daily on days 1-14 plus  oxaliplatin 130 mg/m2 IV on day1; then every 21d until progression or toxicity [17] or

  • Leucovorin 400 mg/m2 IV infused over 2h prior to 5-FU plus  5-FU 400 mg/m2 IV bolus on day 1, followed by 2400 mg/m2 IV infused over 46h plus  oxaliplatin 100 mg/m2 IV on day 1; then every 14d until progression or toxicity [18, 19] or

  • Capecitabine 1250 mg/m2 PO twice daily on days 1-14 plus  cisplatin 60 mg/m2 IV on day 1; then every 21d until progression or toxicity [20] or

  • 5-FU 1000 mg/m2/day via continuous IV infusion on days 1-5 plus  cisplatin 100 mg/m2 IV on day 2; then every 4wk until progression or toxicity [21]

Single-agent regimens for patients with poorer performance status (ECOG score > 2) [16] :

  • Gemcitabine 1000 mg/m2 IV on days 1 and 8; then every 21d until progression or toxicity [22, 23] or

  • Capecitabine 1000 mg/m2 PO twice daily for 14d; then every 21d until progression or toxicity [13] or

  • 5-FU 425 mg/m2 IV bolus plus  folinic acid 20 mg/m2 IV; then weekly until progression or toxicity [24] or

  • Docetaxel 100 mg/m2 IV; then every 21d until progression or toxicity [25]

Special considerations

See the list below:

  • Chemotherapy should generally be reserved for patients with good performance status.

  • Palliative biliary drainage is often necessary in patients with advanced unresectable biliary tract carcinoma.

  • Percutaneous biliary drainage is usually more successful and has a lower complication rate than endoscopic stenting. [26]

  • For patients with unresectable intrahepatic cholangiocarcinoma, radioembolization with yttrium-90 microspheres is an alternative treatment option. [27]