Adenocarcinoma of the oesophagus and gastro-oesophageal junction represent a large burden of cancer death in the Western World with an increasing incidence. In the past two decades, the overall survival of patients on a potentially curative treatment pathway has more than doubled due to the addition of perioperative oncological therapies to surgery. However, patients often fail to respond to oncological treatment or struggle to complete their treatment after surgery. In this review, we discuss the current evidence for total neoadjuvant therapy and options for assessment of treatment response.

Oncological surgery is a discipline which closely interacts with other clinical partners and remains in many cases the cornerstone of a curative treatment of solid tumors. Due to the progress in the field of systemic tumor treatment as well as innovations in surgical techniques, the indications in oncological surgery are also changing, such as extended indications for patients with oligometastatic disease. Surgery of metastases has long been established for colorectal cancer and is being further tested for other entities, such as pancreatic and gastric cancer, within randomized controlled clinical trials (e.g. RENAISSANCE and METAPANC). A new challenge is the handling of a clinical complete remission after total neoadjuvant therapy, for example in locally advanced rectal cancer or in esophageal cancer. Here, organ and function preservation are increasingly propagated but should only be performed within clinical trials until stratification enables the identification of patients in whom this concept is oncologically safe. The personalized use of oncological surgery is dependent on the patient, the tumor and on the total multimodal concept.

Gastric and gastroesophageal junction (GEJ) cancers represent an aggressive group of malignancies with poor prognosis even when diagnosed in relatively early stage, with an increasing incidence both in Asia and in Western countries. These cancers are characterized by heterogeneity as a result of different pathogenetic mechanisms as shown in recent molecular analyses. Accordingly, the understanding of phenotypic and genotypic correlations/classifications has been improved. Current therapeutic strategies have also advanced and moved beyond surgical extirpation alone, with the incorporation of other treatment modalities, such as radiation and chemotherapy (including biologics). Chemoradiotherapy has been used as postoperative treatment after suboptimal gastrectomy to ensure local disease control but also improvement in survival. Preoperative chemoradiotherapy/chemotherapy has been employed to increase the chance of a successful R0 resection and pathologic complete response rate, which is associated with improved long-term outcomes. Several studies have defined various chemotherapy regimens to accompany radiation (before and after surgery). Recently, addition of immunotherapy after trimodality of gastroesophageal cancer has produced an advantage in disease-free interval. Targeted agents used in the metastatic setting are being investigated in the early setting with mixed results. The aim of this review is to summarize the existing data on trimodality approaches for gastric and GEJ cancers, highlight the remaining questions and present the current research effort addressing them.