Perineural invasion through the sheath in posttherapy esophagectomy specimens predicts poor survival in patients with esophageal squamous cell carcinoma

Background: The prognostic impact of perineural invasion (PM) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear. Methods: A thorough pathological review of PM was performed on post-nCRT esophagectomy specimens obtained from non-ypTO patients with esophageal squamous cell carcinoma (ESCC). When PM was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PM surrounding the nerve sheath [PNI-SS] versus PM penetrating through the nerve sheath [PNI-TS]). The impact of PM on overall survival (OS) was assessed in combination with clinical and pathological risk factors. Results: A total of 177 eligible patients were identified between 1998 and 2008. PM was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PM-SS and PM-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PM (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PM-SS (26%, P = 0.68). Multivariate analysis identified PNI-TS (hazard ratio [HR] = 1.965, P = 0.02), LVI (HR = 1.514, P = 0.048), and ypN2 stage (HR = 2.39, P = 0.007) as independent adverse prognostic factors for OS. Conclusions: The presence of PM-TS after nCRT is associated with poor survival. A thorough assessment of distinct PM patterns (i.e., PNI-TS versus PM-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients. (C) 2017 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.