Current Evidence and Future Directions in the Management of Stage II Gallbladder Cancer

Gallbladder cancer (GBC) is an aggressive malignancy with poor overall prognosis, often diagnosed incidentally or at an advanced stage.Optimal outcomes depend on accurate staging, high-quality surgery, and risk-adapted adjuvant therapy.Stage II disease (T2N0M0) remains potentially curable; however, recurrence rates after resection are substantial, highlighting the need for optimized multidisciplinary management.The 8th edition of the American Joint Committee on Cancer TNM staging system subdivided the T2 stage based on tumor location into T2a (peritoneal side) and T2b (hepatic side), reflecting important biological and surgical differences.T2b tumors demonstrate more aggressive biology, with higher rates of lymphatic spread, hepatic micrometastasis, and worse survival compared to T2a tumors.Emerging evidence suggests a potential role for neoadjuvant therapy in selected high-risk patients, although robust prospective data are lacking.Adjuvant chemotherapy with capecitabine for six months remains the current standard of care following R0 resection, based on the Capecitabine for Biliary Cancer (BILCAP) data.Multidisciplinary decision-making is essential, and future studies should focus on refining patient selection for perioperative therapies and integrating new biomarkers and novel therapeutics into clinical practice.This review is intended to document the current evidence and issues for the management strategies for both incidental and non-incidental Stage II GBC.We also discuss the risk-stratified approaches, as no completed Phase III randomized controlled trials specifically dedicated to Stage II incidental GBC currently exist.Furthermore, most of the information relies on retrospective series grouping all biliary tract cancers together, including a limited number of patients with incidentally diagnosed GBC (iGBC).