Perineural Invasion Affects the Risk and Pattern of Recurrence in Non-Small Cell Lung Cancer

OBJECTIVES: We evaluated the impact of perineural invasion (PNI) on recurrence risk and patterns in patients with non-small-cell lung cancer (NSCLC). METHODS: We retrospectively analysed 5545 patients who underwent curative resection for pathologic stage I-III NSCLC between 2009 and 2021. PNI was defined as the presence of tumour cells within nerve sheath layers or tumour foci involving ≥33% of the nerve's circumference. After stratifying patients by PNI status, we compared recurrence-free survival and recurrence patterns. RESULTS: PNI was identified in 290 patients (5.3%), with prevalence increasing by stage (1.8%, 11.6%, and 18.7% in stages I, II, and III, respectively). The PNI (+) group included higher proportions of males and smokers, had lower pulmonary function, higher maximum standardized uptake value (SUVmax), more advanced pathological stage, and increased prevalence of squamous cell carcinoma and other pathologic invasiveness markers. The cumulative incidence of recurrence (CIR) was significantly higher in the presence of PNI (5-year CI: 42.4% in the PNI (+) group vs 16.5% in the PNI (-) group; Gray's test, P < 0.001). Stage-stratified multivariable analysis demonstrated that PNI increased recurrence risk in stages I-II (P < 0.001 and P = 0.021, respectively), but not in stage III (P = 0.245). This trend was consistent in the interaction analysis (P < 0.001). In the recurrence pattern analysis, extrathoracic recurrence was more frequent when PNI was present (P = 0.002). CONCLUSIONS: PNI is associated with an increased risk of recurrence in NSCLC, particularly in early-stage disease. When PNI is present, extrathoracic recurrence is observed more frequently. IRB NO. : B-2101-658-107 (Dec. 23, 2024).