Management of Esophago-Gastric Junction (EGJ) cancer with locoregional disease is an area of ongoing discussion and debate, since there is a paucity of randomized trials focusing exclusively on EGJ cancer. Most of the data that guide the multimodality treatment of EGJ adenocarcinoma are derived from trials that involve predominantly gastric or esophageal cancers. Within the trials designed primarily for gastric cancer, patients with EGJ tumors have accounted for only about 20% of all enrollees. There are epidemiologic and pathobiologic differences between EGJ and noncardia gastric adenocarcinomas that raise concern as to whether results from predominantly gastric cancer trials can be extrapolated to EGJ tumors. Similarly, there are histological differences amongst distal esophageal and EGJ tumors. In Siewert’s original description, he recommended that Type 1 EGJ cancers should be treated as esophageal and Type 2 and 3 treated as gastric cancer.1,2 NCCN guidelines based on the seventh edition of the AJCC staging recommends Type 1 and 2 tumors to be staged and treated as esophageal cancer and Type 3 as gastric cancer.3,4 In the following review, we will discuss the available data supporting the operative and multimodality management of EGJ cancers.
STUDIES FOCUSING ON EGJ CANCER
In 1998, Stahl et al5 conducted a phase II trial wherein 25 patients with locally advanced (T3-T4 NX M0) squamous cell or adenocarcinoma of the lower esophagus or EGJ were treated with two courses of six weekly administrations of 5-Fluorouracil (2.0 g/m2, 24-hour infusion) and folinic acid (500 mg/m2, 2-hour infusion) combined with twice weekly cisplatin (50 mg/m2, 1-hour infusion). Irradiation of 30 Gy was given concurrently with one course of cisplatin and etoposide. Toxicity was most frequently mild to moderate (WHO grade 1 and 2) with mucositis as the most important side-effect of the preoperative treatment. In total, 94% and 88% completed the chemotherapy and chemoradiotherapy according to the protocol, respectively. Sixteen patients underwent complete resection and 10 of the 16 patients had a complete pathological response. They concluded that an intensive preoperative chemoradiotherapy program is feasible and effective in patients with locally advanced carcinomas of the lower esophagus or EGJ. Although this trial had patients with squamous cell carcinoma of the lower esophagus, it was a precursor study to a more specific evaluation in EGJ adenocarcinoma.
Subsequently, the same investigators conducted a phase III trial6 to investigate whether preoperative combined chemoradiotherapy improves the prognosis compared to chemotherapy alone in patients with locally advanced adenocarcinoma of the EGJ. Patients with locally advanced (uT3-4NXM0) adenocarcinoma of the lower esophagus or gastric cardia were randomly allocated to one of two treatment groups: induction chemotherapy (15 weeks) followed by surgery (arm A); or chemotherapy (12 weeks) followed by chemoradiotherapy (3 weeks) followed by surgery (arm B). Primary outcome was overall survival. A total of 354 patients were needed to detect a 10% increase in 3-year survival from 25% ...