SHAPE-ENDO: Pilot Randomized Trial of Multimodal Pre-Surgical Optimization Versus Standard Surgery in Patients With Obesity and Early-Stage Endometrial Cancer

Obesity is a major modifiable risk factor for endometrial cancer and is associated with increased surgical complexity, higher perioperative morbidity, anesthetic risk, and worse functional recovery. Although surgery remains the standard treatment for atypical endometrial hyperplasia and early-stage endometrioid endometrial cancer, patients with grade III obesity may experience a higher risk of perioperative complications. In operable patients with low-risk endometrial disease and BMI ≥40 kg/m², a structured pre-surgical optimization strategy could improve metabolic and functional status before surgery while maintaining oncologic safety through close surveillance. The SHAPE-ENDO strategy combines semaglutide-based metabolic optimization, local hormonal therapy with a levonorgestrel-releasing intrauterine device with or without oral progestins, structured nutritional support, adapted physical exercise, and scheduled histologic and radiologic monitoring. This pilot randomized trial will compare standard immediate surgery with the SHAPE-ENDO multimodal pre-surgical optimization strategy. The aim is not to replace surgery, but to evaluate whether a protocolized and closely monitored optimization window before surgery is feasible, safe, acceptable, and potentially associated with improved perioperative outcomes. Participants in both arms will undergo long-term clinical and oncologic follow-up for at least 5 years after randomization.