Lymphovascular invasion and extracapsular invasion are risk factors for distant recurrence after preoperative chemoradiotherapy and oesophagectomy in patients with oesophageal squamous cell carcinoma

Abstract

OBJECTIVES: Patients with oesophageal squamous cell carcinoma have a high risk of disease recurrence even after trimodality treatments, which include preoperative chemoradiotherapy and oesophagectomy. We aimed to identify the histological factors that are associated with loco-regional and distant recurrence. METHODS: A retrospective review of a prospectively established database identified patients who received preoperative chemoradiotherapy and oesophagectomy for squamous cell carcinoma. The impact of histological factors, including surgical resection margins, lymphovascular invasion (LVI), perineural invasion (PNI), extracapsular invasion (ECI) and tumour regression grade (TRG), on disease recurrence was analysed. RESULTS: A total of 116 patients treated between 2009 and 2015 were included. Sixty-one patients developed disease recurrence, including 25 loco-regional and 49 distant recurrences, with a median disease-free interval of 6 months. Positive histological surgical resection margins were significantly associated with loco-regional recurrence, whereas pre-treatment N stage, ypT stage, ypN stage, positive surgical resection margins, TRG, LVI, PNI, ECI and TRG were significant prognostic factors for distant recurrence. Upon multivariate analysis, cN stage [hazard ratio (HR): 4.049; 95% confidence interval (CI): 1.242-13.200, P = 0.020], LVI (HR: 3.658; 95% CI: 1.891-7.078, P < 0.001) and ECI (HR: 2.393; 95% CI: 1.202-4.763, P = 0.013) remained independent factors for distant recurrence. The 1- and 3-year freedom from distant recurrence rates were 71.8 and 65.6%, respectively, when both LVI and ECI factors were absent, compared to 17.6 and 14.1% when either or both were present (P < 0.001). CONCLUSIONS: Patients with lymphovascular invasion and extracapsular invasion are at a high risk of distant recurrence after preoperative chemoradiotherapy and oesophagectomy. Effective systemic therapy and intensive surveillance are necessary in this group of patients.