INTRODUCTION: While postoperative adjuvant chemotherapy (AC) is generally recommended for intrahepatic cholangiocarcinoma (ICC), its benefit remains debated. This study aimed to identify patients that may benefit from AC following liver resection of ICC. METHODS: Patients who underwent liver resection for ICC between 2000 and 2023 were identified from an international multi-institutional database. Individual multivariable Cox models were used to evaluate the interaction between each prognostic factor and the effect of AC on survival. RESULTS: Among 1412 patients, 431 (30.5%) received AC. Both higher tumor burden score (TBS
hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.91-1.00
p = 0.033) and metastatic lymph node status (HR 0.58, 95% CI 0.38-0.89
p = 0.014) demonstrated interactions with the survival benefit from receipt of AC. Interaction plots highlighted how AC was associated with improved survival beyond a TBS of approximately 6. Notably, among 555 (39.3%) patients with TBS <
6 and N0 or Nx status, 5-year overall survival (OS) was no different between patients who received AC versus individuals who did not (55.1% [95% CI 48.9-62.1] vs. 58.7% [95% CI 49.8-69.2]
p = 0.900). In contrast, among 857 (60.7%) patients with TBS ≥6 or N1 status, AC was associated with improved 5-year OS (30.7% [95% CI 26.2-36.0] vs. 33.0% [95% CI 26.9-40.5]
p = 0.018). CONCLUSIONS: TBS and lymph node status may be useful in a multidisciplinary setting to inform decisions about AC planning for ICC patients following curative-intent resection.