Oncologic impact of perineural invasion in perihilar cholangiocarcinoma: an international multicenter study

Background: We sought to evaluate the prognostic significance of perineural invasion (PNI) among patients undergoing curative-intent resection for perihilar cholangiocarcinoma (pCCA), with a specific focus on early-stage disease. Methods: Data from patients who underwent curative-intent resection for pCCA were collected from eight high-volume international hepatobiliary centers. The association between PNI status, clinicopathological features, and long-term survival was analyzed in both the overall cohort and a subset of patients with early-stage pCCA. Results: Among 435 patients, 364 (83.7 %) were PNI-positive. At the time of surgery, 53 patients with PNI underwent margin re-resection; only 19 (35.8 %) achieved a final R0 margin, whereas 34 (64.2 %) had a persistent R1 margin on the final pathological examination. PNI was independently associated with worse overall survival in the entire cohort (HR 1.52), as well as among patients with T1/2 (HR 1.53) and node-negative (HR 1.60) disease. Although not associated with improved survival among node-negative patients, adjuvant chemotherapy provided a survival benefit among patients with node-negative disease who had PNI (50.8 months vs. 28.6 months; p = 0.044). Conclusion: PNI was an independent predictor of long-term survival, particularly among patients with early-stage pCCA.