FLOT, MAGIC or CROSS for adenocarcinoma of the oesophagus and cardia?

Abstract

Adjunctive treatment with perioperative chemotherapy or neoadjuvant chemoradiotherapy in addition to surgery improves long term survival for patients with operable gastroesophageal adenocarcinoma. Although epirubicin, cisplatin and fluoropyrimidine based chemotherapy was previously a standard of care based on the MAGIC trial, following presentation of the results of the FLOT4/AIO study anthracycline containing regimens have been superseded by taxane based FLOT chemotherapy (docetaxel, oxaliplatin and 5-fluorouracil). Neoadjuvant chemoradiotherapy with carboplatin and paclitaxel as used in the CROSS regimen results in comparable survival to perioperative chemotherapy, however no large randomised trials have directly compared perioperative chemotherapy vs. neoadjuvant chemoradiotherapy in terms of overall survival. This question is being addressed in several ongoing international randomised studies. Currently both perioperative chemotherapy and neoadjuvant chemoradiotherapy are recommended by international guidelines. Whether there are specific groups of patients who may benefit more or less from either treatment has yet to be determined, as is the optimal partner for addition of targeted or immunotherapies. There is still significant room for improvement in treating patients with operable gastroesophageal adenocarcinoma, as regardless of the treatment paradigm, more than half of patients who undergo potentially curative surgery will relapse and die from their disease. Emerging data suggests that risk stratification using easily identifiable biomarkers such as postoperative lymph node status, R0 resection, and the presence or absence of mismatch repair deficiency might allow for a more personalised approach, both in the pre- and postoperative setting. The aim of this presentation is to review the available data on treatment for oesophageal and proximal gastric adenocarcinomas with a view to determining the best treatment for individual patients.