Chemoradiotherapy for esophageal cancer: current status and perspectives.
The optimal role of chemoradiotherapy in the multimodality treatment of esophageal cancer is still controversial. According to a series of clinical trials, definitive chemoradiotherapy is considered the standard of care for patients with medically inoperable or surgically unresectable esophageal cancer. This modality provides survivals comparable to those in Western series of surgery alone and is one of the standards of care even for resectable-stage disease. Recent reports of primary chemoradiotherapy from Japan suggest survival comparable to that of surgery in Japanese patients with stage I disease, but radical surgery is still the standard treatment for T2-3NanyM0 disease in Japan. However, it is clear that this approach has limitations in treatment outcomes. Trimodality therapy, i.e., preoperative chemoradiotherapy followed by surgery, is more favored than surgery alone in clinical practice, particularly in patients with adenocarcinoma, although current data from randomized trials are insufficient to support this approach. To improve the local control rate of chemoradiotherapy, intensification of the radiation dose has been attempted, but this has failed to demonstrate any superiority in terms of local control or survival. The addition of new agents, including molecular targeting agents, to the current standard chemoradiotherapy has shown more promising results and warrants further investigations in future studies. Salvage treatment for patients who do not achieve a complete response (CR) is necessary to improve the overall treatment results. Salvage surgery, as well as endoscopic resection, in selected patients, may provide an improvement in survival. Until high rates of local control can be consistently achieved with chemoradiotherapy alone, these salvage treatments will be an integral component of multimodality treatment for esophageal cancer, and should be active areas for clinical investigations.