ORIGINAL ARTICLE Lymphovascular Invasion as the Major Prognostic Factor in Node-Negative Esophageal Cancer After Primary Esophagectomy Chung-Ping Hsu 1,2 & Cheng-Yen Chuang 3 & Po-Kuei Hsu 1,4 & Ling-I Chien 5 & Chih-Hung Lin 3 & Yi-Chen Yeh 1,6 & Han-Shui Hsu 1,4 & Yu-Chung Wu 1,4 Received: 21 April 2019 /Accepted: 12 June 2019 # 2019 The Society for Surgery of the Alimentary Tract Abstract Background Studies addressing both lymphovascular invasion (LVI) and perineural invasion (PNI) in patients with esophageal squamous cell carcinoma (ESCC) treated with or without neoadjuvant therapy are limited. We aimed to analyze the incidence and prognostic significance of LVI and PNI in patients with thoracic ESCC. Methods This retrospective study included 520 patients with ESCC: 174 patients after neoadjuvant treatment followed by surgery and 346 after primary esophagectomy, from two medical centers. The relationships between LVI, PNI, and other histological factors were evaluated. The Cox regression model was used for survival analysis. Results Positive LVI and PNI were noted in 35.6% and 22.4% of patients with residual primary tumor after neoadjuvant treatment and in 39.6% and 24.0% of patients who underwent primary esophagectomy, respectively. In patients with neoadjuvant treatments, the 5-year overall survival rates were 12.7% and 28.3% in patients with positive LVI and negative LVI, respectively (p = 0.001). The 5-year overall survival rates were 6.4% and 29.9% in patients with positive PNI and negative PNI, respectively (p < 0.001). In patients who did not receive neoadjuvant treatment, the 5-year overall survival rates were 28.2% and 61.1% in patients with positive LVI and negative LVI, respectively (p < 0.001). The 5-year overall survival rates were 30.2% and 52.5% in patients with positive PNI and negative PNI (p < 0.001). In subgroup analysis, the presence of PNI was an independent prog- nostic factor in patients with neoadjuvant treatments, whereas the presence of LVI had more significant prognostic impact in patients with node-negative ESCC after primary esophagectomy. Conclusions Both LVI and PNI statuses are significant prognostic factors for patients with ESCC. However, the prognostic impact of LVI was majorly in the subgroup of node-negative patients who received primary esophagectomy. Keywords Esophageal cancer . Squamous cell carcinoma . Prognosis Introduction Esophageal cancer is one of the most-aggressive cancers with a high recurrence rate after curative treatment. Even in the early stages, treatment failure is common after radical surgery such as transthoracic esophagectomy with extended lymph node dissection, and the prognosis remains poor. 1,2 Multidisciplinary treatment, including combinations of che- motherapy, radiotherapy, and surgical resection, has been in- troduced to reduce systemic micrometastasis and increase the complete resection rate in locally advanced esophageal cancer. Although the efficacy of multidisciplinary treatment has been demonstrated by prospective randomized trials, a significant proportion of patients still experience disease recurrence after trimodal treatment. 3,4 In addition to the depth of tumor inva- sion and the extent of lymph node involvement, 5,6 several Chung-Ping Hsu, Cheng-Yen Chuang and Po-Kuei Hsu contributed equally to this work. * Chung-Ping Hsu cliffhsu@gmail.com 1 School of Medicine, National Yang-Ming University, Taipei, Taiwan 2 Division of Thoracic Surgery, Department of Surgery, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, 707, Sec 3, Chung-Yang Rd., 970 Hualien, Taiwan 3 Division of Thoracic Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan 4 Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan 5 Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan 6 Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan Journal of Gastrointestinal Surgery https://doi.org/10.1007/s11605-019-04310-0