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 (PNI) in patients with esophageal cancer who receive neoadjuvant chemoradiotherapy (nCRT) remains unclear. Methods A thorough pathological review of PNI was performed on post-nCRT esophagectomy specimens obtained from non-ypT0 patients with esophageal squamous cell carcinoma (ESCC). When PNI was identified, it was classified according to the presence or absence of penetration through the nerve sheath (i.e., PNI surrounding the nerve sheath [PNI-SS] versus PNI penetrating through the nerve sheath [PNI-TS]). The impact of PNI 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. PNI was identified in 43.5% (77/177) of participants. Of them, 33 and 44 had PNI-SS and PNI-TS, respectively. The 5-year OS rate of patients with PNI-TS was significantly lower (6.7%) than that observed in those without PNI (30.6%, P < 0.001). However, the 5-year OS observed in the latter group did not differ significantly from that of patients with PNI-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 PNI-TS after nCRT is associated with poor survival. A thorough assessment of distinct PNI patterns (i.e., PNI-TS versus PNI-SS) should be part of the routine post-nCRT histopathological work-up of ESCC patients.