A Multicenter Retrospective Study on Adjuvant S-1 Chemotherapy Versus Observation Following Major Hepatectomy for Perihilar Cholangiocarcinoma.

Background: The prognosis of perihilar cholangiocarcinoma (PHC) is poor even after curative resection, highlighting the need for effective adjuvant chemotherapy. The efficacy of adjuvant S-1 chemotherapy following major hepatectomy for PHC is unclear, and thus the aim of this study was to elucidate this.

Methods: Consecutive patients with PHC who underwent major hepatectomy (hemihepatectomy or trisectionectomy extending to segment 1 with extrahepatic bile duct resection) at three high-volume centers in Japan from 2007 to 2020 were retrospectively evaluated. Patients with Clavien-Dindo grade V complications, pStage 0, I, or IVB disease, and those who underwent adjuvant radiation therapy were excluded from analysis. Propensity score matching analysis was performed to compare the disease-specific survival (DSS) of patients who underwent adjuvant S-1 chemotherapy with those who underwent observation.

Results: Overall, 373/480 patients were eligible, of whom 81 underwent adjuvant S-1 chemotherapy and 146 underwent observation. In the global cohort, DSS was similar in the S-1 and observation groups (p = 0.18), while in the matched cohort (S-1, n = 44; observation, n = 44), DSS was similar between the S-1 and observation groups (p = 0.09). On multivariate analysis, percutaneous biliary drainage (PTBD), CA19-9 levels of ≥ 300 U/mL at operation, and lymph node (LN) metastasis were independent predictors of poor survival following major hepatectomy for PHC. In subgroup analysis of patients with LN metastasis, DSS was better in the S-1 group than in the observation group (p = 0.001).

Conclusions: Adjuvant S-1 chemotherapy following major hepatectomy might be effective in PHC patients with LN metastasis.