Neoadjuvant Treatment of Esophageal and Gastro-Esophageal Cancer

Abstract

The incidence of adenocarcinoma of the esophagus and gastroesophageal (GE) junction has increased rapidly in Western countries, while numbers of squamous cell carcinoma (SCC) have gradually declined. For locally advanced esophageal cancer, surgery remains the mainstay of treatment. However, esophagectomy is historically associated with relatively high rates of irradical resection margins and high numbers of patients presenting with recurrent disease within 2 years after surgery. Therefore, the last decades several multimodality treatment regimens have been developed. Numerous studies evaluated the value of neoadjuvant as well as adjuvant strategies, especially chemotherapy and chemoradiation. In most countries advanced esophageal cancers are treated nowadays by neoadjuvant multimodality treatment regimens. It is thought that neoadjuvant chemotherapy and neoadjuvant chemoradiation eliminate micrometastases and induce locoregional tumor regression which leads to a higher rate of radical esophagectomies due to a reduction in the number of R1 and R2 resections (downstaging). However, its value has been debated for several decades. Up to a few years ago, the majority of the studies did not show any statistically significant benefit for neoadjuvant therapy, but these studies were frequently criticized because of inadequate trial design, limited statistical power (small sample size), and poor outcomes in the surgery alone group. However, in recent years, many different neoadjuvant regimens have been developed and tested. Historically, in the United Kingdom neoadjuvant chemotherapy was advocated while in Continental Europa and the USA neoadjuvant CRT was the preferred treatment. Ultimately the question which modality is superior will hopefully be answered by the Neo-AEGIS study, which compares perioperative chemotherapy (MAGIC) with neoadjuvant chemoradiation (CROSS). This trial design is discussed later on. The present chapter focuses on the different neoadjuvant treatment regimens.