Efficacy of lymph node dissection by node zones according to tumor location for esophageal squamous cell carcinoma

A comprehensive registry of esophageal cancer in Japan has been maintained by the Japan Esophageal Society since 1976. All patient data, including demographic characteristics, symptoms, clinical stage, treatment features, and survival information, were collected. Surgical features, clinical and pathological stage, and detailed lymph node metastatic status were also collected for patients who underwent surgery.

A total of 24,748 patients with primary esophageal tumor treated in 2004, 2005 and 2006, and 2007 and 2008 were registered in 2011, 2012, and 2014, respectively, from 239 institutions in Japan [3‐7]. Of the 24,748 patients, 22,667 had primary thoracic esophageal tumor, excluding cervical esophageal tumor and Siewert type II and type III esophagogastric junction cancers [8]. Of the 12,408 patients who underwent esophagectomy, 11,136 underwent R0 resection, and patients who underwent R1 and R2 resections were excluded due to limited node dissection. Of the 11,136 patients who underwent R0 resection, 4820 (43.3 %) patients underwent esophagectomy with three-field lymph node dissection [9, 10]. For the purpose of evaluating the frequency of metastasis to all regional node areas precisely, only the patients who underwent esophagectomy with three-field lymph node dissection were selected. The cervical, mediastinal, and abdominal lymph nodes were dissected. Dissections of supraclavicular nodes and cervical paraesophageal nodes were required for cervical dissection by three-field dissection in the registration. Since it was based on a multi-institutional, nationwide registry, the selection of patients and indications for three-field dissection depended on each institution and each surgeon, and were not specified. The three-field dissection was performed in 60.5 % of patients with upper esophageal tumor, 49.5 % of patients with middle esophageal tumor, and 30.8 % of patients with lower esophageal tumor. It was performed in 36.5 % of patients with cT1 tumor and 48.2 % of patients with cT2-4 tumor. Of the 4820 patients who underwent esophagectomy with three-field lymph node dissection for R0 resection, information about the locations of pathological metastatic lymph nodes was available for 4083 patients, and outcome evaluations were available in 4004 patients. Of the 3956 patients excluding 48 patients who received definitive chemoradiotherapy and underwent salvage esophagectomy, 3827 patients (97 %) had squamous cell carcinoma including adenosquamous carcinoma and basaloid squamous carcinoma, 64 patients (1.6 %) had adenocarcinoma, and 65 patients had other tumors including undifferentiated tumor, carcinosarcoma and malignant melanoma. The total study group comprised 3827 patients who underwent R0 resection and esophagectomy with three-field lymph node dissection for squamous cell carcinoma from 155 institutions (Fig. 1).

Clinical stages for all patients were recorded according to the 6th edition of the UICC TNM Classification [11]. Pathological stages for all patients were re-assessed according to the 7th edition of the UICC TNM Classification [1]. The thoracic esophagus was divided into three anatomical subsites: upper, middle, and lower. The tumor location is regarded as the point of deepest tumor invasion according to the Japanese Classification [12], which in clinical practice is the epicenter of the tumor.

The areas of lymph node metastasis were recorded according to the lymph node stations adopted by the Japanese Classification [12]. There are some differences in the definition of lymph node stations between the Japanese Classification [12] and AJCC Staging Manual [2] (Table 1). This difference in the anatomical definition of each lymph node station might have influenced the nodal categorization. However, with the database collected, there was no way to reasonably reconcile or amend such differences. So, lymph node stations were classified into lymph node zones according to the map in AJCC Staging Manual [2] (Table 1). The middle mediastinal zone and the lower mediastinal zone were divided by caudal margin of the inferior pulmonary vein.

To evaluate the efficacy of nodal dissection at each zone, the efficacy index (EI) was calculated by multiplying the frequency (%) of metastases to a zone and the 5-year survival rate (%) of patients with metastases to that zone, and then dividing by 100 [13‐15]. The EI was investigated according to tumor location. The EI was also determined by clinical T factor: cT1 and cT2-4. Survival rates were constructed using the Kaplan–Meier method. Statistical analysis was performed using the SPSS Statistics Software Package (SPSS Inc., Chicago, IL, USA).