# Potential Survival Benefit of Adjuvant Chemotherapy in Stage IV Intrahepatic Cholangiocarcinoma: A Multicenter, Stage‐Stratified Analysis

## TL;DR

This study finds that adjuvant chemotherapy, especially S-1, may improve survival for stage IV intrahepatic cholangiocarcinoma patients after surgery.

## Contribution

The study identifies a survival benefit of adjuvant chemotherapy in stage IV ICC and highlights S-1 as a potentially effective regimen.

## Key findings

- Adjuvant chemotherapy improved survival in stage IV ICC but not in earlier stages.
- S-1 chemotherapy showed significantly better outcomes compared to other regimens in stage IV ICC.
- Poor liver function and lymph node metastasis were identified as adverse prognostic factors in stage IV ICC.

## Abstract

The survival benefit of adjuvant chemotherapy (AC) in intrahepatic cholangiocarcinoma (ICC) remains uncertain, particularly in advanced‐stage disease.

We retrospectively analyzed 480 patients who underwent curative‐intent hepatic resection for ICC at eight institutions between 2006 and 2023. Patients were stratified by receipt of AC, and survival outcomes were compared across LCSGJ stages. Multivariable Cox regression was used to identify prognostic factors.

Among 480 patients, 206 received AC. While AC did not significantly improve survival in stage I–III disease, it was associated with significantly longer overall survival (median 25.5 vs. 17.1 months, p = 0.008) and recurrence‐free survival (median 10.3 vs. 6.0 months, p = 0.010) in stage IV patients. Multivariable analysis in stage IV revealed that AC independently reduced the risk of death (HR 0.540, p = 0.020), while poor liver function, severe postoperative complications, tumor size, and lymph node metastasis were adverse prognostic factors. Among AC regimens, S‐1 demonstrated significantly longer OS (69.3 vs. 17.1 months, p = 0.001) and RFS (9.6 vs. 6.0 months, p = 0.015) compared with no AC, whereas other regimens did not show statistically significant benefits.

Adjuvant chemotherapy was associated with improved survival in patients with resected stage IV ICC. Among available regimens, S‐1 appeared to contribute to this benefit. These findings support the use of AC in advanced ICC and suggest that S‐1 may play a potential role, warranting further prospective validation. Stage‐specific treatment planning may be essential to optimize outcomes.

This multicenter study suggests that adjuvant chemotherapy may improve survival in stage IV intrahepatic cholangiocarcinoma after resection, with S‐1 showing a potential survival advantage.