SHAPE-ENDO: Multimodal Pre-Surgical Optimization in Patients With Obesity and Early-Stage Endometrial Cancer (Phase 1)

Brief Summary

SHAPE-ENDO is a prospective, single-center, low-intervention, non-randomized, single-arm clinical trial conducted at Hospital Universitari de Bellvitge (Barcelona, Spain). The study is designed to evaluate a protocolized multimodal pre-surgical optimization strategy in women with severe obesity (BMI ≥40 kg/m²) and atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial cancer. The strategy is intended for selected patients in whom immediate surgery may be associated with increased perioperative risk due to obesity and comorbidities. Participants will receive a structured multimodal optimization program aimed at improving metabolic and functional status while maintaining local oncologic control. The multimodal strategy includes authorized treatments used according to clinical indication, product labeling, current guidelines, and physician judgment: semaglutide/GLP-1 receptor agonist therapy for metabolic optimization, local hormonal treatment with a levonorgestrel-releasing intrauterine device with or without oral progestins, structured nutritional intervention, adapted physical exercise, and scheduled clinical, imaging, and histological surveillance. The primary objective is to estimate the proportion of participants who achieve predefined pre-surgical optimization criteria after the multimodal strategy, including clinically relevant weight loss and/or reduction to BMI \<40 kg/m², absence of tumor progression, and acceptable anesthetic/surgical risk. Secondary outcomes include histological response, metabolic and anthropometric changes, treatment adherence, safety, health-related quality of life, feasibility of subsequent surgery, perioperative outcomes, and exploratory long-term survival outcomes. Participants will be followed during a 28-54 week optimization period. Long-term follow-up will assess recurrence, survival, quality of life, and metabolic outcomes. Exploratory adjusted comparisons may be performed against a historical cohort of patients with similar baseline characteristics previously treated at the same institution.