A layered risk framework for non-benchmark intrahepatic cholangiocarcinoma after curative-intent resection: an international multi-institutional analysis.

BACKGROUND

Surgical benchmark (BM) values define attainable perioperative outcomes after curative-intent resection for intrahepatic cholangiocarcinoma (iCCA), yet non-benchmark (non-BM) patients remain poorly characterized. Whether tumor biology refines prognosis beyond BM status remains unclear.

METHODS

Patients undergoing curative-intent resection for iCCA at international centers (2000-2023) were classified using published BM criteria. Non-BM patients were stratified as surgical-axis only, medical-axis only, or dual-axis. A five-component biology risk score, tumor burden score (TBS), and BM status were evaluated for overall survival (OS).

RESULTS

Among 1794 patients, 1128 (62.9%) were non-BM. Non-BM iCCA met 6 of 11 benchmark cutoffs, although readmission, severe complications, and 90-day mortality exceeded thresholds. Five-year OS differed between BM and non-BM patients (45.4% vs 37.1%; p < 0.001), but not across non-BM axes. Within non-BM, ≥2 biology risk factors were associated with worse OS (aHR 2.29, 95%CI 1.53-3.44). Five-year OS ranged from 52.8% in BM/low-TBS to 29.1% in non-BM/high-TBS. Biology score remained associated with OS across BM status (aHR 1.34 per factor, 95%CI 1.17-1.54).

CONCLUSION

Non-BM iCCA comprised most resected patients and met several benchmark cutoffs. Surgical and medical axes captured perioperative complexity without refining long-term prognosis, whereas TBS and pathologic biology provided additional oncologic stratification.