Updated 20 January 2006

1 Surgery

The only curable option for gallbladder cancer is surgery. Absolute contraindications to surgery include non-contiguous liver or peritoneal metastases, ascites, extensive involvement of the hepatoduodenal ligament, and encasement or occlusion of major vessels. Direct involvement of the colon, duodenum, or liver is not an absolute contraindication.

Simple cholecystectomy is generally sufficient for patients with T1a lesions. T1a lesions have an incidence of lymph node metastases of only 2.5%. Muscle invasive lesions (stage T1b) are associated with a 15% incidence of lymph node metastases. These tumors may be better treated with radical or extended cholecystectomy which would include removal of the gallbladder plus at least 2 cm of the gallbladder bed, and lymphadenectomy that includes the regional lymph nodes from the hepatoduodenal ligament beyond the second portion of the duodenum, head of the pancreas and the celiac access. Patients with stage ll or lll disease treated with an extended cholecystectomy including resection of a 3 to 5 cm wedge of liver, resection for N1 and N2 nodes, and resection of extra hepatic bile ducts have the best chance of long term survival. Extended cholecystectomy candidates should be referred to a tertiary center and surgeon with expertise in this procedure.

Implantation of carcinoma at biopsy sites is a concern. These should be resected at the time of surgery.

Patients with locally advanced but resectable disease should undergo radical surgery. Although their prognosis is still poor, reports have suggested longer survival in patients undergoing such surgery.

Surgical debulking is rarely performed for patients with locally advanced unresectable disease Jaundice can usually be managed non-operatively with a stent placement or external beam radiotherapy.

If a patient is diagnosed with gallbladder cancer incidentally at the time of cholecystectomy, re-exploration and radical resection is warranted if the disease is greater than or equal T2. The benefit of re-exploration for patients with incidentally diagnosed T1 disease is more controversial but could be considered for healthy patients where the tumor invades the muscularis layer (T1b).

2 Adjuvant Radiotherapy

The benefit of adjuvant radiotherapy both alone or with chemotherapy after resection of gallbladder cancer has not been tested in randomized controlled studies. At this time there is no evidence of a clear survival benefit.

3 Adjuvant Chemotherapy

Retrospective series have suggested a small degree of benefit from adjuvant chemotherapy, however, this is not been observed in prospective trials. Well-designed trials of adjuvant or neoadjuvant chemotherapy are needed. Currently, there is no standard recommendation for adjuvant chemotherapy.

4 Treatment of Unresectable Disease

The prognosis of unresectable and metastatic disease is poor, with median survivals of less than one year.

External beam radiation may be used for palliative management of locally advanced disease. At the time of surgical exploration, the marking of the margins of unresectable tumors with radiopaque clips can facilitate radiation treatment planning. Palliative radiotherapy can be considered for relief of pain in selected patients with residual or recurrent disease.

In patients with locally advanced, unresectable disease, the role of neoadjuvant chemotherapy and radiotherapy remains investigational.

A number of agents have demonstrated activity in phase ll studies in patients with advanced disease. Gemcitabine appears to be the most interesting agent alone or in conjunction with cisplatin. Response rates as high as 50% have been reported for gemcitabine plus cisplatin with the occasional complete response described. At this time, evidence for a survival advantage is lacking. Other active agents (gemcitabine, capcitabine, docetaxel, cisplatin) give response rates of 25-50%, however the optimal regimen has not been defined by randomized trials. In addition, there is no good evidence comparing chemotherapy to best supportive care. The standard BC Cancer Agency approach is cisplatin with infusional 5-fluorouracil (see GIFUC). Gemcitabine may also be considered (undesignated indication).