Multimodal therapy for esophageal squamous cell carcinoma according to TNM staging in Japan-a narrative review of clinical trials conducted by Japan Clinical Oncology Group

Abstract

Objective: To clarify the historical transition of multimodal treatment for esophageal cancer in Japan. Background: Treatment strategies for esophageal cancer in Asian countries often differ from those in Western countries, owing to differences in the proportion of patients with squamous cell carcinoma among all patients with esophageal cancer, available chemotherapeutic agents, surgical techniques employed, etc. In Japan, the treatment strategies are determined based on the results of multicenter trials conducted by the Japan Clinical Oncology Group (JCOG). For early esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT), which is less invasive than surgery, has been demonstrated to be effective in cases of non-curative endoscopic resection (ER). In regard to postoperative adjuvant therapy for cases of advanced ESCC, the emphasis shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy in the 1990s; in the 2000s, the optimal timing of perioperative adjuvant chemotherapy switched from postoperative adjuvant therapy to preoperative neoadjuvant therapy. Recently, the JCOG has completed patient recruitment for a three-arm randomized controlled trial of neoadjuvant therapy [cisplatin + 5-fluorouracil (CF) vs. CF + docetaxel (DCF) vs. CF + radiation therapy (41.4 Gy)] for locally advanced ESCC. Salvage and conversion surgery for ESCC has been developed in Japan, and the JCOG has conducted phase I/II trials to confirm the feasibility and safety of such aggressive surgery. Currently, the JCOG is conducting several clinical trials for different stages of resectable and unresectable ESCC. Methods: We present a review of the Japanese trials conducted for ESCC of different clinical stages. Conclusions: The standard treatment for ESCC in Japan has changed over the years according to the results of clinical trials. The results of future trials may lead to the selection of a better treatment.