Endometrial cancer incidence is rising in lockstep with global obesity rates, and in early-stage disease, women are statistically more likely to die from obesity-related comorbidities than from cancer recurrence itself. This narrative review, conducted using SANRA criteria, synthesizes evidence that minimally invasive metabolic/bariatric surgery (laparoscopic, robotic, endoscopic) combined with hysterectomy is feasible in selected patients with severe obesity and endometrial hyperplasia or carcinoma. Critically, GLP-1 receptor agonists appear to modulate both the obesogenic systemic environment and tumor-associated pathways in endometrial carcinogenesis — though direct antitumor clinical evidence remains unestablished.
The framing here is significant: recontextualizing obesity as an oncologically modifiable risk factor, not merely a surgical complication, represents a meaningful conceptual shift in gynecologic oncology. GLP-1RAs like semaglutide already demonstrate mechanistic plausibility — reducing hyperinsulinemia, systemic inflammation, and estrogen excess, all drivers of endometrial proliferation. However, this is a narrative review, not a meta-analysis or RCT, meaning the evidence hierarchy is limited and subject to selection bias in included studies. No direct antitumor benefit has been clinically confirmed. The call for prospective trials stratified by molecular endometrial cancer subtype (POLE, MMRd, p53-aberrant) is well-placed, as metabolic intervention responses likely vary by tumor biology. For clinicians and health-conscious readers, this signals a near-future integration of metabolic medicine into oncology care pathways — incremental today, but potentially paradigm-shifting as trial data mature.