Simple SummaryEndoscopic ultrasonography is commonly used for the initial staging of esophago-gastric adenocarcinoma. However, the preoperative staging after neoadjuvant therapy remains controversial, with PET-CT and endoscopic ultrasonography suggested but not universally applied. In this study, we examined a large series of gastric and esophago-gastric junction adenocarcinomas, where both procedures were performed as part of the initial staging and after preoperative chemotherapy. Our findings indicate that both EUS and PET-CT have limitations but can determine the stage of cancer and predict survival. Notably, the study showed that the assessment of lymph nodes using endoscopic ultrasonography and the evaluation of response to preoperative chemotherapy were predictive of survival, underscoring the importance of this procedure as an additional tool for staging in this particular setting.AbstractBackground: The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. Methods: We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. Results: A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3–77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8–81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3–73%). Kaplan–Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. Conclusion: Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.