What are the treatment options for gallbladder cancer?

Treatment of Gallbladder Cancer

Surgery is the only curative treatment for gallbladder cancer, with simple cholecystectomy sufficient for Tis and T1a disease, but extended cholecystectomy (radical resection with lymphadenectomy and liver resection) required for T1b and beyond to achieve meaningful survival. 1, 2

Surgical Management by Stage

Early Stage Disease (Resectable)

For Tis and T1a tumors:

• Simple cholecystectomy alone is adequate treatment 3
• No additional resection required if margins are negative 3

For T1b and beyond:

• Extended cholecystectomy is mandatory, which includes: 1, 3
  • En bloc resection of gallbladder
  • Wedge resection of liver segments IVb and V (or formal anatomic resection)
  • Regional lymphadenectomy (hepatoduodenal ligament, periportal, and peripancreatic nodes)
  • Bile duct resection if involved 1

Critical surgical principles:

• Avoid laparoscopic cholecystectomy when malignancy is suspected due to risk of tumor spillage and port-site metastases 3
• Achieve R0 resection (negative margins) as this is the most important prognostic factor 4
• Preoperative staging should include chest imaging, CT abdomen, and consider laparoscopy to detect occult metastases (present in 10-20% at presentation) 1

Adjuvant Therapy After Resection

For high-risk patients after R0 resection:

• Gemcitabine plus cisplatin is the standard adjuvant chemotherapy regimen 2, 5
• This provides approximately 4 months survival benefit and improves quality of life 2
• Consider fluoropyrimidine-based chemoradiation as an alternative option 4

For R1 (microscopic positive margins) or R2 (gross residual) resections:

• Multidisciplinary review is essential 4
• Options include: additional resection if feasible, fluoropyrimidine or gemcitabine-based chemotherapy, or fluoropyrimidine chemoradiation 4

Advanced/Unresectable Disease

First-line systemic therapy:

• Gemcitabine plus cisplatin is the established standard of care 2, 5
• This combination provides 3.6-4 months survival benefit compared to best supportive care 2
• Response rates of 30-50% have been reported 2
• Recent evidence supports adding immune checkpoint inhibitors (durvalumab or pembrolizumab) to gemcitabine-cisplatin for further survival improvement 5, 6

Patient selection for chemotherapy:

• Performance status is the single most important prognostic factor 2
• Treat patients with Karnofsky performance status ≥50 who are not rapidly deteriorating 4, 2
• Initiate treatment early rather than waiting for disease progression 4, 2
• Quality of life should be the primary focus, with survival as secondary endpoint 4, 2

Second-line therapy:

• FOLFOX (5-FU/folinic acid and oxaliplatin) is the only recommended regimen after gemcitabine-cisplatin failure 5
• Molecular profiling should be performed to identify actionable mutations for targeted therapy 5, 6

Palliative Interventions

For biliary obstruction:

• Endoscopic or percutaneous biliary stenting to relieve jaundice 4
• Metal stents preferred if survival expected >6 months; plastic stents if <6 months 4
• Avoid routine preoperative biliary drainage except for acute cholangitis 1

Locoregional therapies for unresectable disease:

• Percutaneous ablation for tumors <5 cm in inoperable patients (median survival 33-38.5 months) 1
• Transarterial chemoembolization (TACE) for advanced disease (median survival 9.1-30 months) 1
• Photodynamic therapy after biliary decompression provides survival benefit 2

Common Pitfalls to Avoid

• Never perform laparoscopic cholecystectomy when gallbladder cancer is suspected due to high risk of tumor dissemination 3
• Do not delay chemotherapy in eligible patients waiting for further progression 2
• Avoid radiation therapy in advanced disease as it has no proven survival benefit and significant toxicity 2
• Do not offer liver transplantation outside clinical trial protocols at specialized centers 2
• Remember that gallbladder cancers can be multifocal (5%), requiring careful margin assessment 1
• Comprehensive staging is mandatory as up to 50% have lymph node involvement at presentation 1

Multidisciplinary Approach

Essential team members: 6, 7

• Surgical oncology for resection decisions
• Medical oncology for systemic therapy
• Radiation oncology for selective cases
• Advanced endoscopists for biliary interventions
• Palliative care specialists for symptom management
• Nutritionists for supportive care