Esophagogastric cancer is among the most common malignancies worldwide. Surgery with or without neoadjuvant therapy is the only potentially curative treatment option. Although esophagogastric resections remain associated with major surgical trauma and significant postoperative morbidity. Prehabilitation has emerged as a novel strategy to improve clinical outcomes by optimizing physical and psychological status before major surgery through exercise and nutritional and psychological interventions. Current prehabilitation programs may be unimodal, including only one intervention, or multimodal, combining the benefits of different types of interventions. However, it still is an investigational treatment option mostly limited to clinical trials. In this comprehensive review, we summarize the current evidence for the role of prehabilitation in modern esophagogastric cancer surgery. The available studies are very heterogeneous in design, type of interventions, and measured outcomes. Yet, all of them confirm at least some positive effects of prehabilitation in terms of improved physical performance, nutritional status, quality of life, or even reduced postoperative morbidity. However, the optimal interventions for prehabilitation remain unclear; thus, they cannot be standardized and widely adopted. Future studies on multimodal prehabilitation are necessary to develop optimal programs for patients with esophagogastric cancer.

The optimal approach for treating cytology-positive (Cy1) gastric cancer (GC) patients without additional non-curative factors remains uncertain. While neoadjuvant chemotherapy followed by gastrectomy shows promise, its suitability for Western patients is not well supported by existing data. To address this knowledge gap, a cohort study was conducted across four major GC treatment centers in Lithuania, Estonia, and Ukraine. Forty-three consecutive Cy1 GC patients who underwent neoadjuvant chemotherapy between 2016 and 2020 were enrolled. The study evaluated overall survival (OS), progression-free survival (PFS), cytology status conversion, and major pathological response rates, along with the factors influencing these outcomes. All patients underwent surgery post-neoadjuvant chemotherapy, with 53.5% experiencing cytological status conversion and 23.3% achieving a major pathological response. The median OS and PFS were 20 (95% CI: 16–25) and 19 (95% CI: 11–20) months, respectively. Conversion to negative cytology significantly reduced the relative risk of peritoneal progression (RR: 0.11; 95% CI: 0.03–0.47, p = 0.002). The study suggests that neoadjuvant chemotherapy followed by gastrectomy holds promise as a treatment option for Cy1 GC without additional non-curative factors, associating cytology status conversion with improved long-term outcomes and reduced peritoneal relapse risk.

Background/Objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis. This study investigates gut microbiome changes throughout GC treatment, including NAC and gastrectomy. Methods: This longitudinal observational study included GC patients undergoing NAC followed by gastrectomy. Fecal microbiome composition, intestinal inflammation (fecal calprotectin), and gut permeability (LBP, sCD14) markers were investigated at baseline, after NAC, and after gastrectomy. Results: A total of 38 patients were included in the study. The results showed that NAC did not affect the gut microbiome composition at the phylum level. In contrast, radical gastrectomy led to an increased abundance of Bacteroidetes and Proteobacteria and a decreased abundance of Firmicutes and Actinobacteria. Furthermore, NAC alone did not impact alpha or beta diversity, while a combination of NAC and gastrectomy significantly influenced both. After gastrectomy, the gut microbiome composition analysis also revealed enrichment of oralization-associated bacterial species such as Escherichia-Shigella, Streptococcus equinus, uncultured Streptococcus species, and species from the Enterobacteriaceae family. Intestinal inflammation and gut permeability markers did not significantly change throughout the treatment. Conclusions: The radical treatment of advanced GC with NAC and radical surgery has long-term effects on the gut microbiome, characterized by gut microbiome oralization. These sustained alterations primarily stem from the radical gastrectomy rather than the NAC. Since previous studies have linked oralization-associated dysbiosis to various gastrointestinal symptoms, this study highlights the gut microbiome as a potential therapeutic target to enhance the quality of life in long-term survivors following gastrectomy.