Liver resection with and without vascular resection versus transplantation for de novo perihilar cholangiocarcinoma

Background & Aims: The optimal treatment strategy for de novo pCCA remains debated. This study compares outcomes between liver transplantation following neoadjuvant chemoradiation (RT+LT) and liver resection (LR), with (LR+VR) and without vascular resection (LR w/o VR). Methods: This single-center, retrospective study included de novo pCCA patients treated at Mayo Clinic Rochester (1993-2023) with curative-intent surgery. Patients underwent either (1) LR, classified as LR+VR or LR w/o VR, or (2) RT+LT following the transplant protocol. Overall survival (OS) and recurrence-free survival (RFS) were analyzed using as-treated (AT) and intention-to-treat (ITT) approaches, incorporating competing risk analysis and direct matching. Results: In the AT analysis, RT+LT showed superior median OS compared to LR w/o VR (78.0 vs. 58.2 mo, p=0.03) and LR+VR (25.8 mo, p<0.001). Considering dropout rates (RT+LT: 41%, LR: 28%), ITT analysis showed no significant OS difference between LR and RT+LT (31.7 vs. 38.5 mo, p=0.19). In matched AT analysis, RT+LT had no significant survival benefit over LR w/o VR (50.6 vs. 140.6 mo, p=0.08) or LR+VR (25.8 mo, p=0.11). Perioperative mortality was 4% (RT+LT), 7% (LR w/o VR), and 8% (LR+VR). Conclusion: Both LR and RT+LT achieve excellent oncological outcomes in selected de novo pCCA patients. Key challenges remain dropouts during neoadjuvant therapy in patients planned for LT and high perioperative mortality for patients undergoing LR. OS doubles in LR+VR patients compared to dropouts, supporting LR+VR as a viable option for LT-ineligible patients. Appropriate patient selection is crucial, as those not undergoing surgery suffer from a dismal prognosis.