Prognostic impact of perineural invasion in intrahepatic cholangiocarcinoma: multicentre study

Background: The aim of this study was to investigate the prognostic impact of perineural invasion (PNI) on tumour recurrence and survival among patients with resected intrahepatic cholangiocarcinoma (ICC). Methods: This was a multicentre, retrospective study of patients who underwent resection with curative intent for ICC between 2000 and 2017. The relationship between PNI, clinicopathological characteristics, and long-term survival was analysed in the overall cohort and the subset of patients with early-stage ICC. Results: Among 1095 patients who underwent resection of ICC, PNI was present in 239 (21.8 per cent). In univariable analysis, PNI was associated with worse disease-free survival (DFS) (median 13.2 versus 16.1 months for patients with and without PNI respectively; P = 0.038) and overall survival (OS) (26.4 versus 41.5 months; P < 0.001). In multivariable analysis, PNI was an independent risk factor associated with reduced DFS (hazard ratio (HR) 1.56, 95 per cent c.i. 1.06 to 2.13; P = 0.019) and OS (HR 1.74, 1.16 to 2.60; P = 0.007). In subgroup analysis of patients with early-stage disease (AJCC T1-2, 981 patients; or N0, 249 patients), PNI remained associated with worse DFS (T1-2: median 13.7 versus 16.6 months in patients with and without PNI respectively, P = 0.019; N0: 11.7 versus 17.5 months, P = 0.022) and OS (T1-2: 28.5 versus 45.7 months, P < 0.001; N0: 34.9 versus 47.5 months, P = 0.036). Conclusion: PNI is a strong independent predictor of tumour recurrence and long-term survival following resection of ICC with curative intent, even among patients with early-stage disease. The presence of PNI should be assessed routinely.