Neoadjuvant Chemotherapy in Advanced Stage Endometrial Cancer: A Systematic Review and Meta-Analysis

<i>Background and Objectives</i>: Endometrial cancer is the most common gynecological malignancy in developed countries and is becoming increasingly prevalent. Early diagnosis and treatment may lead to lower rates of morbidity and mortality. The aim of the present meta-analysis is to investigate whether neoadjuvant chemotherapy (NACT) can enhance resectability, reduce tumor burden, and ultimately improve survival rates compared to primary surgery in patients with advanced endometrial cancer. <i>Materials and Methods</i>: All studies that examined the impact of NACT on survival outcomes of patients with advanced endometrial cancer were eligible for inclusion, including randomized and non-randomized interventional studies. Studies were identified by searching MEDLINE (1945-2024), Scopus (1941-2024), Google Scholar (2004-2024) and ClinicalTrials.gov (2000-2024). Data was selected and extracted by two reviewers based on the PRISMA guidelines. <i>Results</i>: Five retrospective studies with a cumulative total of 8658 patients were included. No statistically significant difference in overall survival was observed between patients who received NACT and those who underwent primary surgery (HR 0.91, 95% CI 0.79-1.04). NACT was associated with some perioperative advantages, though these did not translate into a survival benefit. <i>Conclusions</i>: The currently available evidence, which is limited to retrospective studies with significant heterogeneity, suggests that NACT does not confer a survival advantage over primary debulking surgery in advanced endometrial cancer. These findings should be considered hypothesis-generating, underscoring the need for prospective trials. NACT may still be a reasonable option for selected subgroups, such as frail patients, those with extensive peritoneal disease, or cases in which complete cytoreduction is unlikely with upfront surgery.