Beyond Weight Loss: A Comprehensive Review of Integrated Pharmacotherapy and Metabolic Bariatric Surgery in Endometrial Cancer Care

Backgroundand Objectives: Endometrial cancer ranks among the most prevalent gynecologic malignancies in high-income countries, with increasing incidence and mortality driven by the global obesity epidemic. Evidence suggests that women with early-stage disease face a greater risk of death from obesity-related comorbidities than from cancer recurrence and that weight reduction is associated with improvements in quality of life and in the long-term burden of obesity-related morbidity and mortality. Minimally invasive (MIS) metabolic/bariatric surgery is the most effective treatment for achieving significant, sustained weight loss and comorbidities resolution/improvement. Advances in MIS (laparoscopic, robotic, and endoscopic) techniques have reduced perioperative morbidity and mortality. Novel pharmacotherapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), have recently received regulatory approval for weight management and ongoing studies are investigating their therapeutic impact on endometrial carcinogenesis and tumor biology. This review synthesizes and critically appraises evidence on metabolic interventions, including innovative bariatric techniques and pharmacologic agents, with the aim of informing their integration into multidisciplinary, risk-adapted management strategies for patients with severe obesity and endometrial cancer. Materials and Methods: A comprehensive review was conducted in accordance with SANRA (Scale for the Assessment of Narrative Review Articles) criteria. Results: Emerging evidence indicates that MIS metabolic/bariatric surgery combined with hysterectomy is feasible and may be integrated into the multidisciplinary management of selected patients with severe obesity and endometrial hyperplasia or carcinoma. GLP-1RAs may modulate both the obesogenic systemic milieu and selected tumor-associated pathways, although definitive clinical evidence of direct antitumor effect and oncologic benefit in endometrial cancer has not been established. Conclusions: Obesity is a modifiable risk factor for endometrial cancer. Metabolic/bariatric interventions represent a promising component of the comprehensive, patient-centered management of this disease. Prospective studies are essential to clarify the association between these interventions and longitudinal oncologic outcomes, the feasibility and potential benefits of combined approaches, and their differential impact according to the molecular classification of endometrial cancers. Although weight reduction is associated with a lower risk of endometrial cancer, a direct improvement in cancer-specific survival has not yet been demonstrated; weight-loss management therefore represents a promising component of care in the severely obese population, and its incorporation into formal guidelines requires confirmation in prospective studies.