Bile Duct Cancer: PNI Linked to Survival Outcomes

Perineural invasion (PNI) occurs in approximately one third of patients with resected intrahepatic cholangiocarcinoma (ICC), according to a systematic review and meta-analysis. ICC is a primary liver cancer arising from the bile ducts that is known for aggressive behaviour and often presents at advanced stages.

Across 61 studies involving 15,502 patients, PNI was identified in 36.0% of cases. The analysis also linked PNI with poorer overall survival, while suggesting it may reflect aggressive tumour biology rather than function as an independent prognostic factor.

Perineural Invasion as a Marker of Aggressive ICC Biology

ICC is the second most common primary hepatic malignancy after hepatocellular carcinoma, with incidence increasing worldwide over recent decades. Only around 35% of patients qualify for surgery, the mainstay of curative-intended therapies, while up to 54% have unresectable disease at diagnosis, post-resection recurrence rates remain high at 57.9% to 73.4%. Prognosis after resection remains poor, with a 5-year survival rate of only 20% to 40%.

PNI refers to the spread of cancer cells along or around nerves and is recognised as a marker of tumour aggressiveness in several cancers. However, its frequency and prognostic value in ICC have remained uncertain.

Perineural Invasion Could Support Future ICC Risk Stratification

Researchers followed PRISMA guidelines and analysed studies identified through PubMed, Web of Science and the Cochrane Library up to August 2025. Meta-analysis showed PNI was linked to poorer overall survival, with a pooled hazard ratio of 1.79 (p<0.001). PNI also showed significant positive correlation with lymph node metastasis, lymphovascular invasion and vascular invasion (p<0.001).

The authors highlighted important limitations, including considerable heterogeneity across available research (I² = 98.5%), which may limit interpretation of the pooled estimates. Differences in publication year and study size influenced reported PNI prevalence, and the independent effect of PNI on survival remains unclear.

The findings indicate that PNI assessment could help refine risk stratification and support clinical decision-making and patient counselling in ICC. Further standardised prospective studies are needed to clarify whether PNI has a role in guiding treatment strategies and providing prognostic information beyond established tumour features.

Reference

Kolck J et al. Perineural invasion in intrahepatic cholangiocarcinoma: meta-analysis of prevalence, association with tumor features & impact on survival. JHEP Rep. 2026;DOI: 10.1016/j.jhepr.2026.101939.

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