Impact of perineural invasion as a histopathological prognostic factor in ypStage II/III oesophageal squamous cell carcinoma†

Objectives: The 8th edition American Joint Committee on Cancer Tumour-Nodes-Metastasis (TNM) staging system distinguishes between the clinical (c), pathological (p) and post-neoadjuvant pathological (yp) stage groups. However, the ability to discriminate between ypStage II and ypStage III is poor. We aim to identify prognostic factors in patients with ypStage II/III oesophageal squamous cell carcinoma.

Methods: The data of 150 patients with ypStage II/III oesophageal squamous cell carcinoma from 2 medical centres were retrospectively reviewed. The neoadjuvant treatments included chemotherapy with cisplatin and 5-fluorouracil, administered concurrently with external beam radiation. The determination of perineural invasion (PNI) was based on pathological reports. Survival curves were compared using the log-rank test, and multivariable survival analysis was performed with a Cox regression model.

Results: The 3-year/5-year overall survival rate/median survival in ypStages II, IIIa and IIIb were 35.3%/26.9%/21.9 [95% confidence interval (CI) 14.9-28.8] months, 33.8%/22.5%/22.4 (95% CI 20.1-24.7) months and 21.7%/14.0%/14.4 (95% CI 11.1-17.7) months, respectively (P = 0.07). The 3-year/5-year overall survival rate/median survival was 36.7%/26.4%/22.8 (95% CI 19.2-26.5) months in the absence of PNI and 6.9%/3.4%/9.1 (95% CI 8.9-9.4) months in the presence of PNI (P < 0.001). In the multivariable survival analysis, tumour location in the upper third of the thoracic oesophagus [hazard ratio (HR) 1.692, 95% CI 1.087-2.635; P = 0.020] and positive PNI (HR 3.316, 95% CI 2.005-4.905; P < 0.001) remained as independent prognostic factors.

Conclusions: The existence of PNI after neoadjuvant treatment is closely associated with poor prognosis and could be incorporated into the TNM staging system for better discrimination between patients with ypStage II/III oesophageal squamous cell carcinoma.