Long-term outcomes of preoperative chemotherapy for borderline resectable perihilar cholangiocarcinoma

Resectability in perihilar cholangiocarcinoma (PHCC) is multidimensional, and anatomically advanced disease often necessitates highly complex surgery. Long-term outcomes of anatomically defined borderline resectable (BR) PHCC treated with preoperative chemotherapy remain unclear.

This single-center retrospective cohort study included consecutive patients with PHCC treated between May 2018 and October 2024. Patients with distant metastases were excluded. Among 142 registered patients, 42 were classified as anatomically defined BR according to institutional criteria. BR comprised Bismuth type IV disease requiring trisectionectomy, major vascular invasion requiring arterial and/or portal reconstruction, and distal extension requiring hepatopancreatoduodenectomy (HPD). All patients received gemcitabine-based preoperative chemotherapy followed by reassessment of resectability. The primary endpoint was overall survival (OS) among patients with anatomically defined BR PHCC who received preoperative chemotherapy.

Of 42 patients with BR PHCC, 34 (81.0%) underwent resection, achieving an R0 rate of 73.5%. Resection rates varied by anatomical subtype and were lowest in Bismuth type IV disease (61.9%). Major postoperative complications (Clavien-Dindo ≥3a) occurred in 44.1%, and 90-day mortality was 2.9%. The resected group achieved a 5-year OS rate of 42.9% and a median survival of 36.6 months, compared with 19.4 months in the not-resected group (P = 0.038). For the entire BR cohort, the 5-year OS rate was 38.8%.

In anatomically defined BR PHCC, multidisciplinary treatment with preoperative chemotherapy was associated with favorable clinical outcomes. However, resectability differed across anatomical subtypes, highlighting heterogeneity within anatomically advanced disease. Given the absence of a control group, these findings should be considered descriptive and hypothesis-generating.