Progress in Multimodal Treatment for Advanced Esophageal Squamous Cell Carcinoma: Results of Multi-Institutional Trials Conducted in Japan

SIMPLE SUMMARY: In Japan, the therapeutic strategies for esophageal squamous cell carcinoma (ESCC) are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Since there are several differences in the factors influencing the treatment approach for esophageal cancer between Eastern and Western countries, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. Because a transthoracic esophagectomy with three-field lymph node dissection has been performed as a standard surgical procedure for advanced thoracic ESCC in Japan, multimodal treatment for ESCC has been developed to improve the surgical outcomes after this relatively invasive surgical procedure. In this review, we describe the history and current status of therapeutic strategies for ESCC in Japan with a focus on the results of clinical trials conducted by the JEOG. ABSTRACT: In Japan, the therapeutic strategies adopted for esophageal carcinoma are based on the results of multi-institutional trials conducted by the Japan Esophageal Oncology Group (JEOG), a subgroup of the Japan Clinical Oncology Group (JCOG). Owing to the differences in the proportion of patients with squamous cell carcinoma among all patients with esophageal carcinoma, chemotherapeutic drugs available, and surgical procedures employed, the therapeutic strategies adopted in Asian countries, especially Japan, are often different from those in Western countries. The emphasis in respect of postoperative adjuvant therapy for patients with advanced esophageal squamous cell carcinoma (ESCC) shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy in the 1990s. In the 2000s, the optimal timing of administration of perioperative adjuvant chemotherapy returned from the postoperative adjuvant setting to the preoperative neoadjuvant setting. Recently, the JEOG commenced a three-arm randomized controlled trial of neoadjuvant therapies (cisplatin + 5-fluorouracil (CF) vs. CF + docetaxel (DCF) vs. CF + radiation therapy (41.4 Gy) (CRT)) for localized advanced ESCC, and patient recruitment has been completed. Salvage and conversion surgeries for ESCC have been developed in Japan, and the JEOG has conducted phase I/II trials to confirm the feasibility and safety of such aggressive surgeries. At present, the JEOG is conducting several trials for patients with resectable and unresectable ESCC, according to the tumor stage. Herein, we present a review of the JEOG trials conducted for advanced ESCC.