Immunohistochemistry is NOT Required to Start Chemotherapy for Advanced Gallbladder Cancer
You can and should initiate standard first-line chemotherapy (gemcitabine plus cisplatin plus immunotherapy) immediately upon confirming advanced gallbladder cancer without waiting for immunohistochemistry results. 1
Standard First-Line Treatment Initiation
The current standard of care for advanced gallbladder cancer is gemcitabine 1000 mg/m² plus cisplatin 25 mg/m² on days 1 and 8 of each 21-day cycle, combined with durvalumab 1500 mg on day 1, which can be started based on histologic confirmation of gallbladder adenocarcinoma alone. 2, 1
This regimen provides a median overall survival of 12.9 months versus 11.3 months with chemotherapy alone (HR 0.76,95% CI 0.64-0.91), and delaying treatment to wait for additional testing is not recommended. 2, 1
When IHC May Be Relevant (But Not Required for Starting Treatment)
While IHC is not needed to start chemotherapy, it may be ordered in parallel for specific clinical scenarios:
PD-L1 testing: Not required for treatment decisions, as both TOPAZ-1 and Keynote-966 trials showed benefit regardless of PD-L1 status. 2
Targetable alterations: IHC or molecular profiling for HER2, FGFR, BRAF, and other driver mutations should be sent at diagnosis but should NOT delay chemotherapy initiation, as these are relevant only for second-line or later therapy after progression on first-line treatment. 3
Diagnostic uncertainty: IHC may help distinguish gallbladder adenocarcinoma from other biliary tract cancers or metastases from other primary sites, but this is a pathologic diagnostic issue, not a treatment prerequisite. 3
Critical Timing Considerations
Avoid delaying chemotherapy in eligible patients, as median survival without treatment is only 2.5-6 months, and early initiation correlates with improved outcomes. 1, 4
Patients should be started on treatment if they meet basic eligibility criteria: 4
- ECOG performance status 0-2
- Adequate organ function (creatinine clearance sufficient for cisplatin)
- Optimized biliary drainage if jaundiced
- Not rapidly deteriorating
Common Pitfall to Avoid
The most critical error is delaying treatment initiation while waiting for molecular testing or IHC results that will not change first-line therapy decisions. 1, 4 The survival benefit of adding immunotherapy to chemotherapy applies broadly across the advanced gallbladder cancer population, and molecular profiling results are only actionable after progression on first-line therapy. 2, 3
Pembrolizumab can be substituted for durvalumab as an alternative immunotherapy option, though the benefit in extrahepatic biliary tract cancers (including gallbladder) was less pronounced in Keynote-966 (HR 0.99,95% CI 0.73-1.35) compared to TOPAZ-1. 2