Gallbladder Cancer

Gallbladder cancer is an aggressive biliary malignancy, with adenocarcinoma accounting for most cases.

Many tumours are discovered incidentally after cholecystectomy performed for presumed benign gallstone disease.

Prognosis is determined primarily by depth of invasion, nodal involvement and distant metastatic disease.

An intact oncological resection is essential. Gallbladder perforation or bile spillage during surgery for an unsuspected cancer can disseminate malignant cells within the peritoneum.

Early disease commonly mimics gallstone pathology.

Advanced disease can produce:

• Persistent right upper quadrant pain
• Weight loss
• Anorexia
• Jaundice
• Palpable mass
• Liver involvement

Jaundice frequently indicates advanced hilar or hepatoduodenal ligament involvement and should prompt careful assessment of resectability.

Multiphasic CT chest and abdomen: determine liver invasion, nodal disease, vascular involvement and distant metastases.

MRI with MRCP is useful when biliary or hepatic extension requires further definition.

Staging laparoscopy should be considered before major resection when disease appears locally advanced because occult peritoneal metastases may make laparotomy nontherapeutic.

Incidental Tis or T1a disease

Tumour confined to the mucosa or lamina propria is adequately treated by a complete simple cholecystectomy when margins are negative.

T1b and more advanced localised disease

T1b disease has a meaningful risk of nodal metastasis and should be discussed for completion oncological resection in a fit patient, although the magnitude of benefit from reoperation in T1b remains less certain than for higher stages.

For T2 or selected T3 resectable disease, perform radical resection consisting of:

• Gallbladder bed liver resection, commonly segments IVb and V or an equivalent wedge providing an adequate margin
• Regional portal lymphadenectomy

Aim to retrieve at least six regional lymph nodes for adequate pathological staging.

Routine extrahepatic bile duct resection is unnecessary when the cystic duct and bile duct margins are clear. Resect bile duct only when required to obtain an R0 margin.

Routine port site excision after incidental laparoscopic gallbladder cancer is not required in the absence of port site disease.

Adjuvant treatment

After curative resection of muscle invasive gallbladder or bile duct cancer, a standard adjuvant option is:

Capecitabine 1250 mg/m² orally twice daily on days 1 to 14 of a 21 day cycle for 8 cycles.

Dose modification is required according to renal function and treatment toxicity.

Unresectable or metastatic disease

A current first line regimen is:

• Durvalumab 1500 mg IV day 1
• Gemcitabine 1000 mg/m² IV days 1 and 8
• Cisplatin 25 mg/m² IV days 1 and 8

given every 21 days for up to 8 cycles, followed by:

Durvalumab 1500 mg IV every 4 weeks until progression or unacceptable toxicity.

Perform molecular profiling in advanced disease because mismatch repair deficiency, HER2 alterations and other targetable abnormalities may create additional treatment options.