The Role of Adjuvant Chemotherapy for Localized Squamous Cell Esophageal Cancer: Current Japanese Standard and the Unending Role of the Drawing Board

Abstract

Esophageal cancer is the sixth most common cause of death for men and, among the various gastrointestinal malignancies, it is considered to possess a relatively high malignant potential. Major causes of the difficulties in the management of this clinical entity are largely related to its clinicopathological characteristics, particularly the high frequency of complex patterns of lymph node metastasis. As a result of intense discussion beginning approximately 30 years ago, radical esophagectomy with threefield lymphadenectomy has become established in leading institutes in Asia since the mid 1980 s. Although relatively acceptable long-term outcomes have been reported, one can claim by no means that substantial evidence of survival benefit has been proved by large-scale, randomized, controlled trials (RCT). Even in the high-volume centers in Asia, further improvement of 5-year survival rates by surgery alone appears to be extremely unlikely. Therefore, optimization of multimodal treatments for localized and resectable clinical stage II/III esophageal cancer is one of the most important topics in this field. Several clinical trials in the west have demonstrated the superiority of preoperative chemoradiation therapy compared with surgery alone. However, it must be admitted that one of the most conspicuous features, and one that in the minds of many constitutes a critical limitation of the above-mentioned western studies, has been the extremely poor outcome of the surgery-alone groups. On the other hand, Japanese surgeons believe that the relatively acceptable local tumor control by transthoracic radical esophagectomy obviates the need for preoperative radiation therapy, especially because the inevitable fibrotic changes induced by radiation would negatively affect the quality of the surgical approach. Therefore, many Asian physicians treating patients with esophageal squamous cell carcinoma hesitate to apply directly the presently available results of ‘‘Western evidence’’ to ‘‘Eastern’’ esophageal cancer, in which the environment of latter is different from the former. The Japan Clinical Oncology Group (JCOG) has conducted multicenter, multimodality, prospective, clinical trials for the treatment of esophageal cancer for more than 30 years, giving full regard to these considerations. Recently, a JCOG study (JCOG9907) demonstrated significantly better overall survival after preoperative chemotherapy with two courses of cisplatin plus 5-fluorouracil followed by surgery compared with postoperative chemotherapy for resectable cStageII/III thoracic squamous cell esophageal cancer. Since publication of the results of the JCOG9907 study, preoperative chemotherapy followed by radical esophagectomy has been accepted as the standard therapeutic approach to resectable cStage II/III esophageal cancer in Japan. On the other hand, it cannot be denied that the JCOG9907 study has aroused several controversies among some extremely knowledgeable experts who are seeking to examine and interpret the present study as much scientific rigor as possible. In a recent editorial article, Ajani et al. mentioned problems that they noted in the study design of JCOG9907. As representatives of the JCOG Esophageal Cancer Study Group, we would like to respond to their specific criticisms to encourage further understanding Society of Surgical Oncology 2012