SHAPE-ENDO (Strategic Hormonal Approach & Prehabilitation in Endometrial Cancer): Prospective Observational Study for Metabolic and Surgical Optimization in Patients With Atypical Endometrial Hyperplasia or Early-stage Endometrial Cancer and BMI ≥40 kg/m2. (Phase 1)
Overview
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Sponsor
- Hospital Universitari de Bellvitge
- Enrollment
- 82
- Primary Endpoint
- Proportion of patients achieving predefined metabolic and clinical optimization criteria
Overview
Brief Summary
SHAPE-ENDO is a prospective, single-center, observational cohort study conducted at Hospital Universitari de Bellvitge (Barcelona, Spain), designed to evaluate a multimodal pre-surgical optimization strategy in women with severe obesity (BMI ≥40 kg/m²) and atypical endometrial hyperplasia or early-stage, low-risk endometrial cancer.
This strategy reflects current clinical practice in selected patients in whom immediate surgery may be associated with increased perioperative risk due to obesity and comorbidities. Instead of upfront surgery, patients undergo a structured optimization program aimed at improving metabolic status while maintaining local oncologic control.
The multimodal intervention includes standard-of-care treatments:
- Pharmacological metabolic therapy with glucagon-like peptide-1 receptor agonists (GLP-1 RAs, e.g., semaglutide) or dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs, e.g., tirzepatide), according to clinical indication and availability
- Local hormonal treatment with a levonorgestrel-releasing intrauterine device (LNG-IUD), with or without oral progestins
- Structured nutritional intervention
- Supervised physical exercise program
- Scheduled clinical, imaging, and histological surveillance
The study is structured in two phases:
Phase 1 (prospective cohort phase):
Participants are followed during a 28-54 week prehabilitation period to evaluate the proportion of patients achieving predefined optimization criteria, including significant weight loss, improved metabolic status, adequate anesthetic risk profile, and absence of tumor progression. Secondary outcomes include histological response, treatment adherence, quality of life, and feasibility of subsequent surgical management.
Phase 2 (long-term follow-up and comparative phase):
Participants from the prospective cohort will be followed longitudinally for a minimum of 5 years to assess overall survival, disease-specific survival, recurrence rates, long-term metabolic outcomes, and quality of life. In addition, outcomes will be compared with a historical cohort of patients with similar baseline characteristics (BMI ≥40 kg/m²) previously treated at the same institution, with particular focus on surgical morbidity and survival outcomes.
All interventions are part of routine clinical care and are administered according to current clinical guidelines and physician judgment.
The primary objective of the study is to evaluate whether this multimodal strategy can improve surgical eligibility and reduce perioperative risk without compromising oncologic safety, while potentially impacting long-term survival and quality of life in this high-risk population.
Findings from SHAPE-ENDO may provide evidence to support a paradigm shift toward integrated metabolic and oncologic management in patients with obesity and early-stage endometrial cancer, and may inform future controlled comparative studies.
Detailed Description
Obesity is a major modifiable risk factor for endometrial cancer and is associated with increased surgical complexity, higher perioperative morbidity, and reduced eligibility for minimally invasive surgery. In patients with severe obesity, overall mortality is frequently driven by metabolic and cardiovascular comorbidities rather than by cancer progression. Therefore, strategies aimed at improving metabolic health and functional status may have important implications for both surgical outcomes and long-term prognosis.
In selected patients with atypical endometrial hyperplasia or early-stage, low-risk endometrioid carcinoma, conservative hormonal management is widely used to achieve local disease control. At the same time, pharmacological metabolic therapies-including glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonists (GIP/GLP-1 RAs)-have demonstrated substantial weight loss and cardiometabolic benefits in patients with obesity.
Despite these advances, there is a lack of structured clinical approaches integrating oncologic control with metabolic optimization in this population. In routine clinical practice at our institution, selected patients with severe obesity and early-stage endometrial disease who are not optimal candidates for immediate surgery undergo a multimodal optimization strategy combining hormonal treatment, metabolic therapy, and lifestyle intervention, with close clinical and histological monitoring.
The SHAPE-ENDO study is designed to systematically evaluate this real-world clinical approach. It aims to assess whether such a multimodal strategy can improve clinical condition and surgical eligibility without compromising oncologic control, while potentially impacting long-term outcomes such as survival and quality of life.
This study may contribute to the development of integrated care models addressing both cancer and obesity-related comorbidity in patients with early-stage endometrial disease
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Women ≥18 years old.
- •Histologically confirmed Atypical Endometrial Hyperplasia / EIN or low-risk endometrioid endometrial carcinoma (G1-G2), confined to uterine body.
- •Classified as low/intermediate risk per ESGO-ESTRO-ESP 2025; presurgical stages IA1, IA2 or IB.
- •Negative or focal LVSI (if available).
- •Molecular subgroups: POLEmut, p53wt, MMRd or NSMP ER+.
- •BMI ≥35 kg/m² at inclusion.
- •Acceptance of temporary conservative management and ability to follow multimodal optimization strategy.
- •Ability to understand and sign informed consent.
Exclusion Criteria
- •FIGO stages IA3, IC, II or higher.
- •Positive lymphovascular invasion.
- •High-risk molecular: p53mut or NSMP ER-negative.
- •Non-endometrioid histologies (serous, clear cell, carcinosarcoma, mixed, etc.).
- •Metastatic or extra-uterine disease.
- •Contraindication to GLP-1RA or progestogens.
- •Previous pancreatitis, MEN-2, medullary thyroid carcinoma.
- •Participation in another pharmacological trial.
- •Any condition that in investigator judgment impairs safety or compliance.
Arms & Interventions
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Radiologic Surveillance (MRI and Transvaginal Ultrasound) (Procedure)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Levonorgestrel IUD (Lng-IUD) (Device)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Oral Progestins (Drug)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Dietetic-Nutritional intervention (Behavioral)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Structured Exercise and Prehabilitation Program (Behavioral)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: Endometrial Biopsy With or Without Hysteroscopy (Procedure)
SHAPE-ENDO Cohort
Women with BMI ≥40 and atypical endometrial hyperplasia or early-stage endometrial cancer receiving standard-of-care multimodal management including semaglutide or terzipatide, levonorgestrel-releasing intrauterine device ± oral progestins, personalized nutritional counseling, structured exercise program, and scheduled histological surveillance. No randomization or experimental assignment is performed; the study observes clinical outcomes under routine care.
Intervention: GLP-1 Receptor Agonist; GIP/GLP-1 Receptor Agonist (Drug)
Outcomes
Primary Outcomes
Proportion of patients achieving predefined metabolic and clinical optimization criteria
Time Frame: Up to 12 months
Optimization is defined as achieving ≥12-15% total body weight loss and/or reduction to BMI \<35 without evidence of tumor progression on histologic or radiologic assessment, enabling eligibility for minimally invasive surgery. Metabolic parameters (weight, BMI, waist circumference, HbA1c, blood pressure, and lipid profile) are recorded longitudinally. Progression is assessed through scheduled endometrial biopsy and imaging.
Secondary Outcomes
- Change in Glycated Hemoglobin (HbA1c)(Baseline to 6 months and Baseline to 12 months)
- Histological Complete Response Rate of Endometrial Lesion(Baseline to 6 months and 12 months)
- Proportion of patients reaching eligibility for minimally invasive surgery(Up to 12 months)
- Change in Health-Related Quality of Life Score (SF-36)(Baseline to 12 months)
- Change in Serum Triglycerides(Baseline to 6 months and Baseline to 12 months)
- Incidence of adverse events related to standard-of-care treatments(Baseline to 12 months)
- Perioperative outcomes following minimally invasive surgery(At time of surgery and 30 days postoperatively)
- Changes in anthropometric measures (BMI, waist circumference, visceral adiposity)(Up to 12 months)
- Adherence to GLP-1 therapy, hormonal therapy, diet, and exercise interventions(Baseline to 12 months)
- Change in Fasting Plasma Glucose(Baseline to 6 months and Baseline to 12 months)
- Change in HDL Cholesterol(Baseline to 6 months and Baseline to 12 months)
- Change in LDL Cholesterol(Baseline to 6 months and Baseline to 12 months)
- Change in Blood Pressure(Baseline to 6 months and Baseline to 12 months)
- Change in C-Reactive Protein (CRP)(Baseline to 6 months and Baseline to 12 months)
- Change in Quality of Life Score (EORTC QLQ-C30)(Baseline to 12 months)
- Change in Functional Capacity(Baseline to 12 months)
Investigators
Jorge García Fernández
Specialist in Gynaecology and Obstetrics
Hospital Universitari de Bellvitge