This multicenter prospective randomized clinical trial aims to compare the safety and oncological effectiveness of proximal gastrectomy and total gastrectomy in patients with locally advanced Siewert type II-III gastroesophageal junction cancer. Eligible patients will be randomly assigned to undergo either proximal gastrectomy or total gastrectomy using open, laparoscopic, or robotic surgical approaches according to clinical suitability. The primary outcome of the study is 3-year disease-free survival. Secondary outcomes include postoperative mortality, postoperative complications, and the number of metastatic lymph nodes retrieved. Patients will be followed for up to five years after surgery to evaluate long-term oncological outcomes.

Gastroesophageal junction cancers represent a challenging oncological entity, particularly in patients with locally advanced Siewert type II-III tumors. Total gastrectomy has traditionally been considered the standard surgical treatment; however, proximal gastrectomy has gained increasing interest in recent years due to potential advantages in postoperative functional outcomes and reduced surgical morbidity. Nevertheless, concerns remain regarding the adequacy of oncological clearance and lymph node dissection with proximal gastrectomy.

This multicenter prospective randomized clinical trial is designed to evaluate the safety, feasibility, and oncological outcomes of proximal gastrectomy compared with total gastrectomy in patients with locally advanced Siewert type II-III gastroesophageal junction cancer. Patients diagnosed through endoscopic and histopathological evaluation and deemed operable after multidisciplinary tumor board discussion will be included. Following informed consent, participants will be randomized in a parallel design to undergo either proximal gastrectomy or total gastrectomy with D2 lymph node dissection (D2 lymphadenectomy). Surgical procedures may be performed via open, laparoscopic, or robotic approaches based on surgeon preference and patient suitability.

Baseline demographic characteristics, perioperative variables, pathological findings, postoperative morbidity and mortality, and long-term oncological outcomes will be prospectively recorded. The primary endpoint is 3-year disease-free survival (DFS), while secondary endpoints include postoperative complications, mortality, and the number of metastatic lymph nodes. Patients will be followed at predefined intervals for up to five years after surgery. The results of this study are expected to provide high-level evidence to guide surgical decision-making in the management of locally advanced gastroesophageal junction cancers.

Inclusion Criteria:

• Age between 18 and 90 years
• Histologically confirmed locally advanced Siewert type II-III gastroesophageal junction cancer
• Considered operable after multidisciplinary tumor board evaluation
• Candidate for curative surgical resection with D2 lymphadenectomy
• Provision of written informed consent

Exclusion Criteria:

• Early-stage gastroesophageal junction cancer
• Gastric cancers located in the antrum or corpus
• Severe anesthetic risk (American Society of Anesthesiologists [ASA] class IV or higher)
• Pregnancy
• Patients unwilling or unable to provide informed consent

De-identified individual participant data, including baseline characteristics, perioperative variables, pathological findings, and analyzable outcome data, may be shared with qualified researchers after completion of the study and publication of the primary results. Data sharing will be subject to institutional policies, ethical approvals, and applicable data protection regulations.

Due to the nature of surgical interventions, surgeons and patients cannot be fully blinded to the procedure. However, outcome assessment and data analysis will be performed by independent investigators who are blinded to treatment allocation.