Abstract Background Borderline resectability in perihilar cholangiocarcinoma (pCCA) has largely been defined anatomically, although anatomy alone may not capture oncologic risk. This study evaluated whether biologic burden improves recurrence stratification after curative-intent resection of pCCA. Methods Using an international, multi-institutional database, patients undergoing resection without neoadjuvant therapy for non-metastatic pCCA were identified. Literature-based borderline resectability was defined as lymph node metastasis with portal vein/hepatic artery involvement or Bismuth type IV disease. Using a 200-U/mL carbohydrate antigen (CA19-9) cutoff, a three-tier anatomic-biologic borderline resectable (AB-BR) grouping (low, intermediate, high) was derived. The outcome of interest was recurrence-free survival (RFS). Results Among 239 patients (median age, 67.0 years, interquartile range IQR, 58.0–74.0 years), 38.9% ( n = 93) of patients were anatomically borderline resectable (BR). The anatomy-only BR definition did not stratify RFS or overall survival (OS) (both p > 0.05), whereas CA19-9 ≥200 U/mL stratified 2 year RFS within both resectable (55.7% vs. 32.6%) and BR (44.5% vs. 25.3%) groups (all p < 0.05). Four-group analysis demonstrated overlap between resectable/high CA19-9 and BR/low CA19-9, supporting collapsing the categories into AB-BR tiers. The 2 year RFS was 55.7, 37.8, and 25.3% in the low-, intermediate-, and high-risk AB-BR groups, respectively ( p = 0.002). The 2 year area under the curve (AUC) value was improved by AB-BR for RFS versus anatomy alone (0.612 vs 0.537). After multivariable adjustment, high-risk AB-BR remained independently associated with higher hazards of recurrence or death (adjusted hazard ratio, 1.86; 95% confidence interval, 1.15–3.00). Conclusion Anatomic BR alone provided limited prognostic stratification. Incorporating CA19-9 improved recurrence prediction and identified an intermediate-risk group not captured by anatomy alone, supporting biologic resectability in pCCA. The AB-BR framework may help move surgical decision-making beyond technical resectability alone toward more oncologically informed treatment selection.
Chatzipanagiotou et al. (Thu,) studied this question.