Neoadjuvant and Adjuvant Therapy

Multidisciplinary treatment with surgery, chemotherapy, and radiotherapy has become the standard approach for improving outcomes in patients with esophageal cancer. While pivotal trials can encourage the development of optimal clinical practices, the results of clinical trials available in Western countries are not applicable to clinical practices related to esophageal cancer in Asia due to significant East–West differences in this field. In Japan, the emphasis on adjuvant therapy for patients with squamous cell carcinoma (SCC) shifted from postoperative radiotherapy in the 1980s to postoperative chemotherapy, with cisplatin as a key drug in the 1990s. In the late 2000s, the optimal timing for perioperative adjuvant therapy reverted to preoperative treatment, based on the findings of a Japan Clinical Oncology Group study (JCOG9907) comparing preoperative chemotherapy with cisplatin and 5-fluorouracil (CF) to postoperative chemotherapy. During that same era, neoadjuvant chemoradiotherapy (nCRT) followed by surgery became the standard treatment. For neoadjuvant chemotherapy (nCT), triplet preoperative chemotherapy with docetaxel plus CF (DCF) demonstrated promising efficacy in treating locally advanced esophageal SCC (ESCC). The clinical question of whether nCT or nCRT was superior still needed to be clarified. Therefore, the Japan Esophageal Oncology Group launched a three-arm randomized controlled trial, JCOG1109, which enrolled 601 patients with resectable ESCC; the study reported a superior 3-year overall survival (OS) in the neoadjuvant DCF group compared to the neoadjuvant CF group. In contrast, no significant difference in OS was observed between the CF and CF plus radiation groups. Based on these results, neoadjuvant DCF therapy plus surgery became the new standard treatment strategy in Japan. Clinical trials incorporating immune-checkpoint inhibitors into perioperative multimodal treatment for esophageal cancer could help establish the next standard treatment for ESCC.