Biological Selection Explains Survival Differences in Perihilar Cholangiocarcinoma: Post-hoc Application of the Mayo Criteria to a Resection Cohort

Introduction: Survival differences reported across treatment strategies for perihilar cholangiocarcinoma (pCCA) may be strongly influenced by biological patient selection rather than treatment modality itself.This study quantified how much of survival after curative-intent liver resection for pCCA can be explained by biological selection alone, using the Mayo Clinic eligibility criteria as a validated selection framework.Methods: A post-hoc analysis of consecutive patients undergoing liver resection for pCCA between January 2005 and December 2023 at a tertiary referral center was performed.Patients were stratified according to whether they fulfilled adapted Mayo Clinic eligibility criteria (MC).Overall survival (OS) and recurrence-free survival (RFS) were analyzed using Kaplan-Meier estimates and Cox regression.Results: A total of 305 patients were included, of whom 54 (17.7%) met MC.Patients within MC were significantly younger, had lower ASA scores and significantly lower postoperative complications compared with patients outside MC (p < 0.05).Median overall survival was 4.1 years within the MC versus 2.2 years in patients outside the MC (p=0.004).Similarly, median recurrence-free survival was 3.6 versus 1.5 years, respectively (p=0.005).In multivariate analysis, MC was not an independent predictor for overall survival or recurrence-free survival.Instead ASA III, renal failure, coronary artery disease, nodal involvement and positive resection margin was associated with worse survival. Conclusions:When applied to a surgical PCCA cohort, the Mayo eligibility criteria identify patients with markedly improved survival.The survival difference became smaller after adjusting for known prognostic factors.This suggests that the Mayo criteria reflect favorable tumor biology and patient health rather than directly determining outcomes.