What are the treatment options for gallbladder cancer?

Gallbladder Cancer Treatment

Complete surgical resection with extended cholecystectomy, en bloc hepatic resection, and lymphadenectomy is the only potentially curative treatment for gallbladder cancer, and should be pursued aggressively in all resectable cases. 1, 2

Staging and Preoperative Evaluation

Before any treatment decision, comprehensive staging is mandatory:

• Obtain high-quality cross-sectional imaging (CT or MRI) to assess tumor penetration, organ invasion, vascular involvement, and nodal/distant metastases 2
• Perform chest imaging to exclude pulmonary metastases 2
• Staging laparoscopy is highly recommended before laparotomy for potentially curative resection to identify occult peritoneal or hepatic metastases and avoid unnecessary laparotomy 1, 2
• PET scanning is increasingly useful for detecting distant metastatic disease in otherwise potentially resectable cases 2
• Use TNM 2002 staging system with complete history, physical examination, blood counts, liver function tests, and abdominal imaging 1

Surgical Management by Stage

T1a Tumors (Invades Lamina Propria Only)

• Simple cholecystectomy alone is curative if the gallbladder was removed intact with negative margins 1, 3
• Observation only—no re-resection needed 1

T1b Tumors (Invades Muscle Layer)

• Radical re-resection is highly recommended after complete staging including laparoscopy 1, 2
• Perform cholecystectomy with hepatoduodenal lymph node dissection 3
• Extended cholecystectomy may be considered depending on surgical expertise 3

T2 and Greater (Invades Perimuscular Tissue or Beyond)

The standard operation consists of: 1, 2, 3

• Extended cholecystectomy with en bloc hepatic resection (minimum wedge resection of segments IVb and V to achieve R0 margins) 2
• Lymphadenectomy including porta hepatis, gastrohepatic ligament, and retroduodenal regions 1, 2
• Bile duct excision only when necessary to achieve negative margins—not routinely required 1, 2

Critical surgical principles:

• Major hepatectomy should only be performed when necessary to remove disease, as it increases complications without independent survival benefit 1, 2
• Nodal disease beyond porta hepatis/gastrohepatic/retroduodenal regions (celiac, retropancreatic, interaortocaval) indicates unresectable disease 1, 2
• Surgery should only be performed by surgeons trained in cancer operations 1

Incidentally Discovered Gallbladder Cancer

Found During Surgery

• Perform intraoperative staging immediately 1
• Obtain frozen section of gallbladder 1
• Consider extended cholecystectomy with en bloc hepatic resection and lymphadenectomy depending on resectability and surgeon expertise 1

Found on Pathologic Review After Cholecystectomy

• For T1a: Observe only if tumor margins are negative 1, 2
• For T1b or greater: Perform CT/MRI, chest imaging, and laparoscopy to confirm absence of metastatic disease 1, 2
• If resectable, proceed with hepatic resection and lymphadenectomy with or without bile duct excision 1, 2
• Note: 74% of patients undergoing re-exploration have residual cancer, making re-resection critical 1

Unresectable or Metastatic Disease

Systemic Therapy

• Gemcitabine plus cisplatin is the standard first-line regimen for advanced disease 2, 4
• Gemcitabine plus oxaliplatin is an alternative if cisplatin is contraindicated 2
• Fluoropyrimidine-based chemotherapy after progression on first-line therapy 2
• Clinical trial enrollment is strongly encouraged given limited data 2

Palliative Biliary Drainage

• Biliary stenting via ERCP is the preferred palliative treatment for symptomatic obstruction, as it improves survival and quality of life 5, 2
• Metal stents are preferred over plastic stents if life expectancy exceeds 6 months 5, 2
• Surgical bypass has not been demonstrated superior to stenting 1, 5, 2
• PTC should be available as an alternative when ERCP fails 5
• In complex hilar lesions, MRCP planning before stent placement may reduce post-procedure cholangitis risk 5, 3

Critical pitfall: Routine biliary drainage before assessing resectability should be avoided except for acute cholangitis, as inadequate drainage increases sepsis risk 1, 3

Adjuvant Therapy After Resection

After R0 Resection with Negative Nodes

• Observation alone is acceptable 2
• Consider fluoropyrimidine chemoradiation (except T1b, N0) or fluoropyrimidine/gemcitabine chemotherapy 1, 2
• Clinical trial enrollment is encouraged given limited data 2

After R1/R2 Resection or Positive Nodes

• Multidisciplinary review is required 2
• Options include additional resection, fluoropyrimidine chemoradiation, or fluoropyrimidine/gemcitabine-based chemotherapy 2

Surveillance

• No data support aggressive surveillance protocols 2
• Consider imaging every 6 months for 2 years 2
• Re-evaluate according to initial workup if disease progression occurs 2

Prognosis

Five-year survival rates by stage: 1, 2

• Stage 0: 60%
• Stage I: 39%
• Stage II: 15%
• Stage III: 5%
• Stage IV: 1%

Median survival: 1, 2

• Stage Ia-III: 12 months
• Stage IV: 5.8 months

R0 resection status is the most important predictor of survival 2

Critical Pitfalls to Avoid

• Never attempt radical resection in the presence of peritoneal spread—this represents stage IVB disease requiring systemic therapy, not surgery 2
• Do not perform major hepatectomy or bile duct excision unnecessarily when not required for R0 resection 1, 2
• Do not delay palliative chemotherapy while pursuing multiple surgical opinions in metastatic disease 2
• Do not neglect biliary drainage in symptomatic obstruction 2
• Lymph node involvement is present in 50% of patients at presentation and is associated with poor surgical outcomes 3