Perineural Invasion is a Better Prognostic Indicator than Lymphovascular Invasion and a Potential Adjuvant Therapy Indicator for pN0M0 Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) at pN0M0 can be more locally aggressive and disseminated than those with lymph node and distant metastasis. Perineural invasion (PNI) is reported as a poor prognostic factor in cancer and is thought to be related to regional tumor spread and metastasis. However, its clinicopathological role and meaning for treatment in pN0M0 ESCC are unknown. We applied scoring methods of PNI and lymphatic and vascular invasion (LI, VI) based on immunohistochemistry staining on tumor tissues of pN0M0 ESCC patients. ROC analyses, Kaplan–Meier analyses, Cox regression, and χ2 test were performed for survival analysis, comparison of PNI with LI and VI, and exploration of the relevance between PNI and other clinicopathological features. Presence of PNI was significantly associated with poor survival in pN0M0 patients, whereas LI and VI were not predictive of outcome (P > 0.05). Neural invasion index (NII), defined as the ratio of the number of tumor-invaded nerves to the total number of nerves per tumor microsection, was the most consistent measure of PNI (P = 0.006, HR = 6.892, 1.731–27.428). Postoperative radiotherapy significantly improved survival in high-NII patients (P = 0.035, HR = 0.390, 0.163–0.936). PNI is an important risk factor for the outcome of pN0M0 ESCC patients. NII can be used for risk assessment and to tailor adjuvant radiotherapy in this population.