Localized adenocarcinoma of the esophagogastric junction--is there a standard of care?

Adenocarcinoma of the esophagogastric junction (AEG) is the most rapidly increasing tumour in the Western world. Most patients present with locally advanced resectable disease and treatment can be curative. However, no accepted standard treatment exists. Cancer specialists frequently differ on optimum treatment strategies. Areas of debate include the aetiology of AEG, TNM staging, type and extent of resection, relative benefits of preoperative chemotherapy versus preoperative chemoradiation (CRT) versus post-operative CRT, use of early PET scan, and integration of targeted therapy. Randomized trials are weakened by underpowered numbers for AEG tumours, and by methodologic flaws. R0 resection and pathologic complete responses (pCR) predict long-term survival, and most treatment strategies target this as a proxy measure of improved outcome. Some preoperative chemotherapy trials show a benefit but the numbers of true AEG tumours in these studies is unclear. The MAGIC study was powered for gastric cancer only, with just 27% of patients having AEG. Compared with chemotherapy alone, preoperative CRT trials show higher rates of pCR. A large randomized study, with significant toxicity, has shown long-term benefit with adjuvant CRT after resection of gastric cancer (20% AEG). An international consensus on the true definition and optimum management of AEG is required. Molecular and imaging biomarkers will play a vital role in future trials. Trimodality therapy is likely to be optimum with surgery shifted to later in the treatment pathway. Rectal cancer provides an analogous paradigm in this regard. As systemic disease is the primary cause of mortality chemosensitivity should be determined early.