Despite advances in perioperative multimodal therapy, prognosis for patients with gastroesophageal adenocarcinoma remains poor, highlighting the need for reliable biomarkers to improve risk stratification and treatment selection. Perineural invasion (PNI) is a recognised histopathological feature of gastrointestinal malignancies associated with advanced tumour progression, yet its prognostic significance in gastroesophageal cancer (GOC) remains poorly characterised.
We conducted a retrospective cohort study that examined the prevalence, clinicopathological associations, and prognostic impact of PNI in a single-centre cohort of 156 patients undergoing curative-intent resection for oesophageal, gastro-oesophageal junction, or gastric adenocarcinoma between 2013 and 2022. Kaplan-Meier survival analysis and log-rank tests were used to assess the associations between PNI and overall survival (OS) and disease-free survival (DFS).
PNI was identified in 53 of 145 evaluable patients (36.6%) and was significantly associated with advanced AJCC stage (p<0.001), incomplete resection (p<0.001), nodal involvement (p=0.003), high-grade tumour differentiation (p=0.002), lymphovascular invasion (p<0.001), and absence of pathological response to neoadjuvant therapy (p=0.014). PNI-positive patients demonstrated significantly shorter median OS compared with PNI-negative patients (31.0 vs 50.4 months; HR 1.72, 95% CI 1.03-2.86, log-rank p=0.036), with three-year OS of 40.7% versus 68.2%, respectively. There was no significant difference in DFS (p=0.188). On multivariable analysis, PNI was not independently prognostic after adjusting for AJCC stage and tumour location. Subgroup analysis restricted to R0-resected patients demonstrated no significant association between PNI and survival.
PNI is a frequent and clinically relevant finding in resected GOC, associated with adverse clinicopathological features and inferior overall survival. These findings suggest that PNI primarily reflects more advanced disease while supporting its routine reporting and warranting prospective evaluation of its role in prognostic stratification and treatment selection.