Conversion surgery for advanced biliary tract cancer in the era of molecularly targeted therapy and immunotherapy: from unresectable disease to multidisciplinary curative strategy

Biliary tract cancer (BTC) is a heterogeneous and highly lethal malignancy, with many patients presenting with locally advanced or metastatic disease unsuitable for upfront curative resection. Advances in chemotherapy, immunotherapy, and molecularly targeted therapy have created opportunities for conversion surgery in selected patients, but its role and optimal selection criteria remain uncertain.

This review examines conversion surgery for initially unresectable BTC, focusing on modern systemic therapy, candidate selection, timing, subtype-specific surgery, locoregional therapy, liver transplantation, and perioperative management. Conversion rates, R0 resection, postoperative outcomes, and survival are critically evaluated, together with selection, responder, and immortal-time biases and the lack of prospective evidence. Emerging roles of molecular profiling and circulating tumor DNA are also discussed.

Conversion surgery should be regarded as a dynamic, multidisciplinary treatment continuum integrating systemic therapy, biological selection, reassessment of resectability, individualized surgery, and postoperative management. The optimal candidate is identified by the convergence of technical resectability, durable disease control, favorable tumor biology, and adequate physiological reserve. Molecular alterations may guide systemic therapy but should not independently indicate surgery. The goal is to identify the right patient, at the right biological moment, for the right operation.