Comparison of overall survival across treatment modalities for oesophageal, gastroesophageal, and gastric cancer: protocol for a systematic review and network meta-analysis.

backgroundCancers of the oesophagus, gastroesophageal junction (GEJ), and proximal stomach share epidemiological, molecular, and therapeutic characteristics. Despite their similarities, treatment guidelines vary, and the classification of GEJ tumours remains debated. While multiple meta-analyses have addressed subsets of these malignancies, a comprehensive synthesis comparing all treatment modalities across this disease spectrum is lacking. This study aims to perform a systematic review and network meta-analysis (NMA) to compare the overall survival outcomes of different treatment modalities, including surgery, chemotherapy, chemoradiotherapy, immunotherapy, and multimodal approaches, in patients with oesophageal, GEJ, and gastric cancers. METHODS AND ANALYSIS: We will conduct a systematic literature search in MEDLINE (PubMed) and The Cochrane Library (CENTRAL) without date restrictions. Randomised controlled trials (RCTs) comparing eligible treatments will be included. The primary outcome will be overall survival, defined as time from diagnosis to death from any cause. Secondary outcomes will include progression-free survival, disease-specific survival, dropout rates, treatment-related adverse effects, patterns of relapse, R0 resection rates, surgical morbidity, and mortality. We will look for individual patient data (IPD) from primary studies' authors and registries. We will assess risk of bias with the Cochrane risk of bias RoB2 tool. We plan to present each pairwise comparison with risk ratios and 95% confidence intervals from random-effects meta-analysis. A random-effects NMA model will simultaneously compare all treatments in the network. We will rank interventions using P-scores. In case we manage to access IPD and we believe the transitivity assumption does not hold for a specific comparison (or we have a disconnected network), we will use population adjustment methods to estimate an indirect treatment comparison. We will apply CINeMA to assess confidence in the findings and we will report results according to PRISMA-NMA. DISCUSSION: Neoplasms of the oesophagus, the gastroesophageal junction, and the stomach are increasingly being studied together in clinical trials, a trend driven by continuous research on their molecular characteristics and shared therapeutic patterns. This NMA aims to pool evidence employing recent advances in meta-analytic models and critically assess the confidence in the results by implementing the CINeMA approach. SYSTEMATIC REVIEW REGISTRATION: Registered in PROSPERO (CRD42025634169).