Current treatment strategies in the United States for esophageal adenocarcinoma rely on the recommendations of the National Comprehensive Cancer Network (NCCN, Plymouth Meeting, PA, USA) guidelines and are generally based on a multidisciplinary team approach tailored to the individual patient’s American Joint Committee on Cancer (AJCC, Chicago, IL, USA) stage, Siewert–Stein classification, co-morbidities, and other factors
[23]. In patients with locally advanced (T3-T4) or cN1-N3 (lymph node metastasis according to clinical evaluation) esophageal tumors, neoadjuvant chemotherapy or chemoradiotherapy plus resection is required, with most centers tailoring this approach based on histologic subtype
[7][24][25]. Traditional dogma and guidelines recommend against attempted curative resection and metastasectomy in patients with cancers that are felt to be unresectable, or in those with distant disease (T4b, any N, or M1), with instead a focus on palliative chemoradiotherapy
[25][26]. However, contemporary literature has somewhat challenged this philosophy. The recent results of the multicenter German AIO-FLOT3 and AIO-FLOT4 studies evaluating locally advanced, resectable tumors of the esophagogastric junction (EGJ) and stomach suggests well-selected patients may benefit from surgery and peri-operative chemotherapy, and indeed has provided rational for further randomized clinical trials in this cohort
[27][28]. These included patients with histologically confirmed, previously untreated, nonmetastatic, operable (>T2, N any, and M0 or any T, N+, and M0), or metastatic (T any, N any, and M1) adenocarcinoma of the stomach or gastroesophageal junction without disease recurrence or uncontrolled medical illness, and with sufficient bone marrow and kidney function
[27]. Additional investigations from subgroup analyses of clinical trials, retrospective patient cohorts, the Japan Clinical Oncology Study, and current RENAISSANCE (AIO-FLOT5) trial also highlight the ongoing debate of surgical intervention in limited metastatic gastric and esophagogastric cancers
[29][30].