Neoadjuvant treatment for incidental gallbladder cancer: A systematic review

Incidental gallbladder cancer (iGBC) diagnosed post-histopathological examination of gallbladders removed assuming benign gallstone disease constitutes a significant proportion of GBC patients. Most iGBC patients present with early-stage disease. The standard care for localized (non-metastatic) iGBC includes a reoperation for complete extended (radical) cholecystectomy involving liver resection and lymphadenectomy, followed by postoperative adjuvant systemic therapy. However, a major drawback of this approach is the high recurrence rate within six months post-radical surgery, which undermines the benefits of the extensive procedure; notably, most recurrences are distant, highlighting the efficacy of systemic therapy. Similar to other gastrointestinal cancers, there appears to be a potential for neoadjuvant systemic therapy (chemotherapy) before reoperative surgery in iGBC cases. The premise that neoadjuvant systemic therapy aids in selecting diseases with more favorable biological characteristics and addresses micro-metastatic disease appears applicable to iGBC as well. This systematic review examines the current evidence supporting or refuting neoadjuvant therapy and discusses criteria for selecting patients who would derive significant benefit, along with proposing an optimal chemotherapy regimen for iGBC patients. Improved outcomes have been reported in patients undergoing reoperation after 4 to 14 weeks following the initial cholecystectomy compared to immediate reoperation. Limited, yet promising, evidence supports the use of 3 to 4 cycles of gemcitabine-based neoadjuvant chemotherapy prior to reoperative surgery in select high-risk iGBC cases.