Gallbladder Cancer: Current Multimodality Treatment Concepts and Future Directions

SIMPLE SUMMARY: Gallbladder cancer is the most common malignancy of the biliary tract and is associated with several risk factors such as female sex, ethnic background, and chronic biliary inflammation. If gallbladder cancer is detected in a localized stage, it can be cured by surgical resection. In advanced-stage disease, chemotherapy can render up to one-third of patients eligible for surgery with better prognosis. For high-risk patients, chemotherapy after surgery can also help to prevent disease recurrence. In non-resectable patients, a chemotherapy regimen of gemcitabine and cisplatin is the current standard of care but might be soon extended by immunotherapy with durvalumab. Since the unique tumor biology of gallbladder cancer harbors the opportunity for molecular targeted therapy approaches, current research has focused on new therapeutic agents that might improve the poor prognosis of advanced disease. ABSTRACT: Gallbladder cancer (GBC) is the most common primary tumor site of biliary tract cancer (BTC), accounting for 0.6% of newly diagnosed cancers and 0.9% of cancer-related deaths. Risk factors, including female sex, age, ethnic background, and chronic inflammation of the gallbladder, have been identified. Surgery is the only curative option for early-stage GBC, but only 10% of patients are primary eligible for curative treatment. After neoadjuvant treatment, up to one-third of locally advanced GBC patients could benefit from secondary surgical treatment. After surgery, only a high-risk subset of patients benefits from adjuvant treatment. For advanced-stage GBC, palliative chemotherapy with gemcitabine and cisplatin is the current standard of care in line with other BTCs. After the failure of gemcitabine and cisplatin, data for second-line treatment in non-resectable GBC is poor, and the only recommended chemotherapy regimen is FOLFOX (5-FU/folinic acid and oxaliplatin). Recent advances with the PD-L1 inhibitor durvalumab open the therapy landscape for immune checkpoint inhibition in GBC. Meanwhile, targeted therapy approaches are a cornerstone of GBC therapy based on molecular profiling and new evidence of molecular differences between different BTC forms and might further improve the prognosis of GBC patients.