Selecting treatment sequence for patients with incidental gallbladder cancer: a neoadjuvant approach versus upfront surgery

At MSKCC, over 50% of the patients presenting with gallbladder cancer have been diagnosed incidentally following elective cholecystectomy for presumed benign disease. While traditional management of incidental gallbladder cancer (IGBC) dictates re-resection with the ultimate goal of achieving cure, surgical decision-making must take into account that this malignancy is characterized by poor tumor biology with frequent distant recurrence. Since early and frequent distant recurrence is the most common cause of surgical failure, the surgical oncologist's goal should be to selectively re-resect only those patients most likely to benefit from an operation. The astute surgeon recognizes the high-risk patients who likely have micrometastatic disease at the time of diagnosis and alters the treatment sequence, delivering neoadjuvant chemotherapy. This strategy acts as a selection tool, as those progressing at distant sites during therapy are spared the morbidity and mortality of surgery and furthermore has the potential to treat micrometastatic disease. However, a chemotherapy first approach must be applied selectively since a poor response risks local progression to unresectability and a decrease in functional status that comes from the toxicities of dual agent chemotherapy that can impair surgical candidacy. To balance these risks and benefits, two other criteria for a neoadjuvant approach must be met: i) reliable identification of those patients who are at high risk of distant recurrence and who are, therefore, most likely to benefit from a systemic therapy first approach and ii) availability of effective chemotherapy options. In this review, we will outline the data and judgement we use to select a treatment sequence at our institution.