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

SHAPE-ENDO (Strategic Hormonal Approach & Prehabilitation in Endometrial Cancer): An Open-Label, Pilot Randomized Clinical Trial Comparing Standard Immediate Surgery Versus a Multimodal Metabolic Optimization and Prehabilitation Strategy Before Surgery in Patients With Atypical Endometrial Hyperplasia or Low-Risk Endometrioid Endometrial Cancer and BMI ≥40 kg/m²

SHAPE-ENDO is a single-center, open-label, pilot randomized clinical trial conducted at Hospital Universitari de Bellvitge in Barcelona, Spain.

The study will evaluate the feasibility, safety, and acceptability of comparing two treatment strategies in women with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and grade III obesity, defined as BMI ≥40 kg/m².

Eligible participants will be randomized in a 1:1 ratio to one of two arms. The control arm will undergo standard immediate surgery according to the institutional clinical protocol. The experimental arm will receive the SHAPE-ENDO multimodal pre-surgical optimization strategy before surgery.

The SHAPE-ENDO strategy includes metabolic treatment with semaglutide/Wegovy®, local hormonal therapy with a levonorgestrel-releasing intrauterine device/Mirena® with or without oral medroxyprogesterone acetate/Progevera®, a structured nutritional program, adapted physical exercise, and scheduled oncologic surveillance with clinical evaluation, imaging, and endometrial biopsy with or without hysteroscopy.

The experimental strategy will initially last 28 weeks. In participants with clinical, metabolic, or anthropometric benefit, adequate tolerance, and no evidence of tumor progression, the strategy may be extended up to 54 weeks before surgery.

The primary objective is to evaluate the feasibility, safety, and acceptability of the randomized trial design. Primary feasibility outcomes include recruitment rate, acceptance of randomization, retention, adherence to the assigned intervention, completion of the SHAPE-ENDO strategy, progression during the optimization period, and the proportion of participants in the experimental arm who reach surgery without tumor progression.

Secondary outcomes include perioperative morbidity, histological response in the experimental arm, metabolic and anthropometric changes, quality of life, treatment adherence, safety and tolerability, and exploratory long-term oncologic outcomes including overall survival, recurrence-free survival, and cancer-specific survival.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Atypical Endometrial Hyperplasia; Endometrial Cancer; Endometrial Cancer Stage I; Obesity & Overweight; Endometrial Intraepithelial Neoplasia; Atypical Endometrial Hyperplasia and Endometrial Carcinoma Stage I; BMI>40; Obesity Grade III
• Intervention / Treatment: Behavioral: Dietetic-Nutritional intervention; Behavioral: Structured Exercise and Prehabilitation Program; Procedure: Endometrial Biopsy With or Without Hysteroscopy; Procedure: Radiologic Surveillance (MRI and Transvaginal Ultrasound); Drug: GLP-1 Receptor Agonist; Device: Levonorgestrel IUD (Lng-IUD); Drug: Oral Progestins; Procedure: Standar upfront Surgery

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jorge Garcia Fernandez, MD; Phone Number: +34 622595644; Email: jorgarciafernan@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Study Population

Adult women with early-stage, low/intermediate-risk endometrioid endometrial cancer or atypical hyperplasia/EIN and BMI ≥35 kg/m² receiving multimodal metabolic-hormonal prehabilitation prior to surgery.

Description

Inclusion Criteria:

• Female participants ≥18 years old.
• Histologically confirmed atypical endometrial hyperplasia/endometrial intraepithelial neoplasia (AEH/EIN) or low-risk endometrioid endometrial carcinoma, grade 1 or 2.
• Disease apparently confined to the uterine corpus, assessed by expert transvaginal ultrasound and/or pelvic magnetic resonance imaging.
• Low- or intermediate-risk disease according to ESGO-ESTRO-ESP 2025 criteria, including presurgical stages IA1, IA2, or IB.
• Negative or focal lymphovascular space invasion, if available.
• Favorable molecular profile, if available, including POLE-mutated, p53 wild-type, MMR-deficient, or NSMP estrogen receptor-positive disease.
• Body mass index ≥40 kg/m² at inclusion.
• Considered a candidate for surgical treatment by the multidisciplinary tumor board.
• Ability to understand and sign written informed consent after receiving oral and written information about the study, including acceptance of random assignment to either standard immediate surgery or the SHAPE-ENDO multimodal pre-surgical optimization strategy.

Exclusion Criteria:

• FIGO stage IA3, IC, II, or higher disease.
• Extensive lymphovascular space invasion, if available.
• High-risk molecular profile, including p53-abnormal/mutated disease or NSMP estrogen receptor-negative disease.
• Non-endometrioid histology, including serous carcinoma, clear-cell carcinoma, carcinosarcoma, mixed histology, or other high-risk histological subtypes.
• Metastatic disease or suspicion of extrauterine disease.
• Considered medically inoperable or "unfit" for surgery because of severe comorbidity, frailty, anesthetic contraindication, or any other clinical reason contraindicating surgical treatment.
• Contraindication to GLP-1 receptor agonist therapy or progestin-based hormonal therapy, including levonorgestrel-releasing intrauterine device or oral progestins.
• Previous pancreatitis, medullary thyroid carcinoma, or multiple endocrine neoplasia type 2.
• Concurrent participation in another interventional pharmacological clinical trial.
• Any condition that, in the investigator's judgment, may compromise participant safety, interfere with protocol compliance, or make participation inappropriate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A - Standard Immediate Surgery; Participants randomized to the control arm will undergo standard immediate surgical treatment according to the institutional protocol of Hospital Universitari de Bellvitge. Surgery will usually include hysterectomy with bilateral salpingo-oophorectomy, sentinel lymph node assessment when indicated and feasible, and minimally invasive or robotic approach whenever technically possible according to clinical judgment. Intervention: Procedure/Surgery - Standard Immediate Surgery Standard surgical management according to institutional practice for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage low-risk endometrioid endometrial cancer. Perioperative outcomes, surgical approach, conversion to laparotomy, estimated blood loss, operative time, hospital stay, transfusion, sentinel lymph node detection, intraoperative complications, and 30-day postoperative complications graded according to Clavien-Dindo will be recorded.	Procedure: Standar upfront Surgery; Standard surgical treatment according to the institutional protocol of Hospital Universitari de Bellvitge for atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage low-risk endometrioid endometrial cancer. Surgery will usually include hysterectomy with bilateral salpingo-oophorectomy, sentinel lymph node assessment when indicated and feasible, and a minimally invasive or robotic approach whenever technically possible according to clinical judgment. Surgical approach, operative time, estimated blood loss, conversion to laparotomy, transfusion, hospital stay, intraoperative complications, 30-day postoperative complications, readmission, and sentinel lymph node detection will be recorded.; Other Names: BSO; Hysterectomy; Standard Surgery; Upfront Surgery
Experimental: Arm B - Experimental: SHAPE-ENDO Multimodal Strategy Before Surgery; Participants randomized to the experimental arm will receive the SHAPE-ENDO multimodal pre-surgical optimization strategy before surgery. The strategy includes semaglutide/Wegovy®, levonorgestrel-releasing intrauterine device/Mirena® with or without oral medroxyprogesterone acetate/Progevera®, structured nutritional intervention, adapted physical exercise, and scheduled oncologic surveillance. The strategy will last 28 weeks initially and may be extended up to 54 weeks if there is clinical, metabolic, or anthropometric benefit, adequate tolerance, and no tumor progression. Intervention: Drug - Semaglutide / Wegovy® Weekly subcutaneous semaglutide administered according to approved labeling, clinical indication, tolerance, and endocrinology assessment, with standard dose escalation up to the tolerated therapeutic dose. Dose, adherence, tolerability, adverse events, and reasons for dose modification or discontinuation will be recorded. Intervention: Device - Levonorgestrel-Releasing I	Behavioral: Dietetic-Nutritional intervention; Personalized hypocaloric diet plan supervised by the clinical nutrition team as part of standard obesity and metabolic management. The program includes caloric restriction based on basal metabolic requirements, with the option of very low-calorie diets (VLCD) for 4-6 weeks in selected cases. Follow-up occurs at regular outpatient visits with recording of weight, BMI, waist circumference, and adherence. This intervention is part of routine clinical care and not assigned experimentally; outcomes are recorded prospectively.; Other Names: Nutritional Counseling; Hypocaloric diet program; Dietary Prehabiilitation; Behavioral: Structured Exercise and Prehabilitation Program; A structured physical exercise program designed to improve functional capacity, aerobic tolerance, and surgical fitness. Program includes supervised or semi-supervised weekly sessions combining aerobic and strength training, typically 3 sessions per week for 30-45 minutes, adapted to baseline performance. The intervention is part of routine clinical care for patients with obesity undergoing surgical preparation and is not assigned experimentally. Data on adherence, tolerance, and functional outcomes are collected prospectively; Other Names: Exercise Prehabilitation; Supervised Physical Activity Program; Combined Aerobic and Strength Training; Procedure: Endometrial Biopsy With or Without Hysteroscopy; Scheduled histological surveillance performed at baseline and at follow-up intervals (typically 14 and 28-54 weeks) to assess local tumor status, including complete response, stability, or progression. Procedures include outpatient endometrial biopsy with optional hysteroscopy based on clinical indication. These evaluations form part of standard clinical care in patients managed conservatively for atypical endometrial hyperplasia or early-stage endometrioid carcinoma and are not assigned experimentally. Data are recorded prospectively to assess disease evolution and surgical eligibility.; Other Names: Hysteroscopy; Histological Surveillance; Endometrial Sampling; Procedure: Radiologic Surveillance (MRI and Transvaginal Ultrasound); Radiologic evaluation using pelvic MRI and transvaginal ultrasound performed as part of routine clinical care to assess uterine disease, myometrial invasion, adnexal status, and treatment response. Imaging is typically performed at baseline to confirm staging and during follow-up when clinically indicated. These imaging modalities are used per standard clinical guidelines and are not assigned experimentally; results are collected prospectively to evaluate disease stability and surgical planning.; Other Names: Pelvic MRI; Transvaginal Ultrasound; Imaging Surveillance; Drug: GLP-1 Receptor Agonist; Weekly subcutaneous semaglutide/GLP-1 receptor agonist therapy administered according to approved labeling, clinical indication, patient tolerance, and endocrinology assessment, with standard dose escalation up to the tolerated therapeutic dose. The intervention is used for weight loss and metabolic optimization in participants with severe obesity. Dose, adherence, tolerability, and reasons for dose modification or discontinuation will be recorded prospectively.; Other Names: Semaglutide; Device: Levonorgestrel IUD (Lng-IUD); Local hormonal therapy using a 52-mg levonorgestrel-releasing intrauterine system placed at baseline or within 14 days after baseline, with ultrasound confirmation of correct placement. The LNG-IUD is used within the protocolized SHAPE-ENDO strategy according to clinical indication, approved labeling, current guidelines, and physician judgment, for local disease control in atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or early-stage, low-risk endometrioid endometrial cancer. Tolerability, continuation, adverse events, and local histological response will be recorded prospectively.; Other Names: LNG-IUD; Drug: Oral Progestins; Systemic hormonal therapy prescribed according to clinical criteria to support local disease control in atypical endometrial hyperplasia or early-stage endometrioid carcinoma. Typical regimens include medroxyprogesterone acetate (400-600 mg/day) or megestrol acetate (160-320 mg/day). Therapy is initiated or escalated when indicated based on tumor burden or suboptimal response to LNG-IUD. Oral progestins may be used within the protocolized SHAPE-ENDO strategy according to clinical indication, approved labeling, current guidelines, and physician judgment. Use, dosing, tolerance, and outcomes will be recorded prospectively.; Other Names: Medroxyprogesterone acetate; Megestrol acetate; Progestin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recruitment Rate	Number of participants enrolled per month during the active recruitment period. This outcome will assess the feasibility of recruiting eligible participants with atypical endometrial hyperplasia/endometrial intraepithelial neoplasia or low-risk endometrioid endometrial cancer and BMI ≥40 kg/m² into a pilot randomized clinical trial.	From study opening to end of recruitment, up to 36 months.
Acceptance of Randomization Rate	Proportion of eligible participants who agree to participate in the trial and accept random assignment to either standard immediate surgery or the SHAPE-ENDO multimodal pre-surgical optimization strategy.	At baseline, before randomization.
Participant Retention Rate	Proportion of randomized participants who complete the planned follow-up required for the main pilot analysis, including surgical treatment and 30-day postoperative assessment, or completion of the assigned intervention period when applicable.	From randomization to surgery and 30 days postoperatively, up to 14 months.
Adherence to the Assigned Intervention	Proportion of randomized participants who comply with the main procedures planned in their assigned arm. In the control arm, this includes undergoing standard immediate surgery and postoperative follow-up. In the SHAPE-ENDO arm, this includes adherence to the multimodal strategy, scheduled visits, oncologic surveillance, and planned reassessment.	From randomization to surgery and 30 days postoperatively, up to 14 months.
Completion of the SHAPE-ENDO Multimodal Strategy	Proportion of participants randomized to the SHAPE-ENDO arm who complete the planned multimodal pre-surgical optimization strategy until the week 28 reassessment and, when applicable, until week 54.	From randomization to week 28 or week 54.
Proportion of SHAPE-ENDO Participants Reaching Surgery Without Tumor Progression	Proportion of participants randomized to the SHAPE-ENDO arm who undergo surgery after the pre-surgical optimization period without histological, radiological, or clinical evidence of tumor progression.	From randomization to surgery, up to 54 weeks.
Incidence of Serious Adverse Events, Tumor Progression, and Study Discontinuation	Frequency of serious adverse events, tumor progression during the optimization period, and reasons for discontinuation or withdrawal from the study. Adverse events will be recorded prospectively and classified according to CTCAE v5.0 when applicable. These events will be described overall and by randomized arm when applicable.	From randomization to surgery and 30 days postoperatively, up to 14 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative Morbidity	Proportion of participants with intraoperative complications and/or clinically relevant postoperative complications within 30 days after surgery, compared between the standard immediate surgery arm and the SHAPE-ENDO arm. Postoperative complications will be classified according to the Clavien-Dindo classification, with clinically relevant complications defined as Clavien-Dindo grade ≥II	At surgery and up to 30 days postoperatively.
Surgical Approach	Proportion of participants undergoing minimally invasive surgery, robotic surgery, conventional laparoscopy, or laparotomy, compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	At surgery.
Conversion to Laparotomy	Proportion of participants requiring conversion from minimally invasive surgery to laparotomy, compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	At surgery.
Operative Time	Duration of surgery measured in minutes, from skin incision to skin closure, compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	At surgery.
Estimated Blood Loss	Estimated intraoperative blood loss measured in milliliters, compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	At surgery.
Length of Hospital Stay	Number of days from surgery to hospital discharge, compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	From surgery to hospital discharge, up to 30 days.
Need for Blood Transfusion	Proportion of participants requiring perioperative blood transfusion, compared between the standard immediate surgery arm and the SHAPE-ENDO arm	At surgery and up to 30 days postoperatively.
Sentinel Lymph Node Detection Rate	Proportion of participants in whom sentinel lymph node mapping is successful, including unilateral and bilateral detection rates when sentinel lymph node assessment is performed. Detection rates will be described and compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	At surgery.
Histological Response in the SHAPE-ENDO Arm	Proportion of participants in the SHAPE-ENDO arm with complete response, stable disease, or tumor progression during the pre-surgical optimization period. Complete response is defined as absence of endometrioid carcinoma or atypical hyperplasia in endometrial biopsy. Stable disease is defined as persistence of the lesion without progression in grade or stage. Progression is defined as progression from atypical endometrial hyperplasia/endometrial intraepithelial neoplasia to endometrioid endometrial carcinoma, increase to grade 3, high-risk histology, or extension beyond the uterine corpus.	Baseline to week 14, week 28, and, if applicable, week 54.
Time to Optimization in the SHAPE-ENDO Arm	Time from randomization to multidisciplinary committee decision indicating that sufficient clinical, metabolic, anthropometric, and oncologic optimization has been achieved to proceed to surgery.	From randomization to week 28 or week 54
Rate of Surgery After SHAPE-ENDO Optimization	Proportion of participants randomized to the SHAPE-ENDO arm who undergo surgery after the pre-surgical optimization strategy.	From randomization to surgery, up to 54 weeks.
Change in Glycated Hemoglobin	Change from baseline in glycated hemoglobin, measured as HbA1c percentage using standard clinical laboratory assays. Changes over time will be described within each arm and compared between the standard immediate surgery arm and the SHAPE-ENDO arm.	Baseline to 6 months and baseline to 12 months.
Change in Fasting Plasma Glucose	Change from baseline in fasting plasma glucose concentration, measured in mg/dL using standard laboratory assays. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Insulinemia and HOMA-IR	Change from baseline in fasting insulin concentration and HOMA-IR, when available. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in FIB-4 Index	Change from baseline in fibrosis-4 index, calculated using age, AST, ALT, and platelet count. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Lipid Profile	Change from baseline in triglycerides, LDL cholesterol, and HDL cholesterol measured using standard laboratory lipid panel testing. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Blood Pressure	Change from baseline in systolic and diastolic blood pressure, measured in mmHg during scheduled clinical visits. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in C-Reactive Protein	Change from baseline in serum C-reactive protein concentration, measured in mg/L using standard laboratory assays. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Body Weight and BMI	Absolute and percentage change from baseline in body weight and body mass index. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Waist Circumference	Change from baseline in waist circumference, measured in centimeters. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months and baseline to 12 months.
Change in Visceral Adiposity by MRI	Absolute and percentage change from baseline in visceral adiposity measured by pelvic MRI according to the predefined radiologic measurement protocol. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to week 28 and, if applicable, week 54.
Change in Body Composition by Bioelectrical Impedance Analysis	Change from baseline in body composition parameters measured by bioelectrical impedance analysis. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to week 28 and, if applicable, week 54.
Change in Health-Related Quality of Life Score - SF-36	Change from baseline in health-related quality of life assessed using the Short Form-36 Health Survey. Scores range from 0 to 100, with higher scores indicating better health-related quality of life. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months, 12 months, and during long-term follow-up up to 5 years.
Change in Quality of Life Score - EORTC QLQ-C30	Change from baseline in quality of life assessed using the EORTC QLQ-C30 questionnaire. Scores range from 0 to 100 according to EORTC scoring guidelines. Changes over time will be described within each arm and compared between both randomized arms.	Baseline to 6 months, 12 months, and during long-term follow-up up to 5 years.
Overall Survival	Time from randomization to death from any cause. Participants alive at the end of follow-up will be censored at the date of last contact.	From randomization up to 5 years.
Cancer-Specific Survival	Time from randomization to death from endometrial cancer. Participants alive or deceased from causes unrelated to endometrial cancer will be censored according to the statistical analysis plan.	From randomization up to 5 years.
Recurrence-Free Survival	Time from randomization to first documented recurrence of endometrial cancer. Recurrence may be defined by histological, radiological, or clinical evidence according to standard follow-up criteria. Participants without recurrence will be censored at the date of last available follow-up.	From randomization up to 5 years.

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Collaborators: University of Barcelona
• Investigators: Principal Investigator: Jorge Garcia Fernandez, Hospital Universitari de Bellvitge; Principal Investigator: Lola Marti, Hospital Universitari de Bellvitge

Publications and helpful links

General Publications

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• Akesson A, Wolmesjo N, Adok C, Milsom I, Dahm-Kahler P. Lymphadenectomy, obesity and open surgery are associated with surgical complications in endometrial cancer. Eur J Surg Oncol. 2021 Nov;47(11):2907-2914. doi: 10.1016/j.ejso.2021.06.034. Epub 2021 Jul 1.
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• Cui J, Zhao YC, She LZ, Wang TJ. Comparative effects of progestin-based combination therapy for endometrial cancer or atypical endometrial hyperplasia: a systematic review and network meta-analysis. Front Oncol. 2024 May 3;14:1391546. doi: 10.3389/fonc.2024.1391546. eCollection 2024.
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• Marnach ML, Butler KA, Henry MR, Hutz CE, Langstraat CL, Lohse CM, Casey PM. Oral Progestogens Versus Levonorgestrel-Releasing Intrauterine System for Treatment of Endometrial Intraepithelial Neoplasia<sup/> J Womens Health (Larchmt). 2017 Apr;26(4):368-373. doi: 10.1089/jwh.2016.5774. Epub 2016 Nov 30.
• Bourou MZ, Matsas A, Valsamakis G, Vlahos N, Panoskaltsis T. The Potential Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists as a Type of Conservative Treatment of Endometrial Cancer in Women of Reproductive Age: A Review of the Literature and a Call for Study. Cureus. 2024 Sep 18;16(9):e69678. doi: 10.7759/cureus.69678. eCollection 2024 Sep.
• Toliver JC, Divino V, Ng CD, Wang J. Real-World Weight Loss Among Patients Initiating Semaglutide 2.4 mg and Enrolled in WeGoTogether, a Digital Self-Support Application. Adv Ther. 2025 Oct;42(10):5010-5022. doi: 10.1007/s12325-025-03325-1. Epub 2025 Aug 6.
• Garvey WT, Batterham RL, Bhatta M, Buscemi S, Christensen LN, Frias JP, Jodar E, Kandler K, Rigas G, Wadden TA, Wharton S; STEP 5 Study Group. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022 Oct;28(10):2083-2091. doi: 10.1038/s41591-022-02026-4. Epub 2022 Oct 10.
• von Gruenigen VE, Tian C, Frasure H, Waggoner S, Keys H, Barakat RR. Treatment effects, disease recurrence, and survival in obese women with early endometrial carcinoma : a Gynecologic Oncology Group study. Cancer. 2006 Dec 15;107(12):2786-91. doi: 10.1002/cncr.22351.
• Vargiu V, Rosati A, Capozzi VA, Sozzi G, Gioe A, Berretta R, Chiantera V, Scambia G, Fanfani F, Cosentino F. Impact of Obesity on Sentinel Lymph Node Mapping in Patients with apparent Early-Stage Endometrial Cancer: The ObeLyX study. Gynecol Oncol. 2022 May;165(2):215-222. doi: 10.1016/j.ygyno.2022.03.003. Epub 2022 Mar 18.
• Habo YK, Habo NK, Elsayed AAR, Basson MD. Risk factors for postoperative complications following hysterectomy in endometrial cancer patients: A systematic review. J Gynecol Obstet Hum Reprod. 2025 Sep;54(7):102964. doi: 10.1016/j.jogoh.2025.102964. Epub 2025 Apr 30.
• Gallos ID, Yap J, Rajkhowa M, Luesley DM, Coomarasamy A, Gupta JK. Regression, relapse, and live birth rates with fertility-sparing therapy for endometrial cancer and atypical complex endometrial hyperplasia: a systematic review and metaanalysis. Am J Obstet Gynecol. 2012 Oct;207(4):266.e1-12. doi: 10.1016/j.ajog.2012.08.011. Epub 2012 Aug 10.
• Aune D, Navarro Rosenblatt DA, Chan DS, Vingeliene S, Abar L, Vieira AR, Greenwood DC, Bandera EV, Norat T. Anthropometric factors and endometrial cancer risk: a systematic review and dose-response meta-analysis of prospective studies. Ann Oncol. 2015 Aug;26(8):1635-48. doi: 10.1093/annonc/mdv142. Epub 2015 Mar 19.
• Concin N, Matias-Guiu X, Cibula D, Colombo N, Creutzberg CL, Ledermann J, Mirza MR, Vergote I, Abu-Rustum NR, Bosse T, Chargari C, Espenel S, Fagotti A, Fotopoulou C, Gatius S, Gonzalez-Martin A, Lax S, Levy B, Lorusso D, Macchia G, Marth C, Morice P, Oaknin A, Raspollini MR, Schwameis R, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Planchamp F, Nout RA. ESGO-ESTRO-ESP guidelines for the management of patients with endometrial carcinoma: update 2025. Lancet Oncol. 2025 Aug;26(8):e423-e435. doi: 10.1016/S1470-2045(25)00167-6.

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): April 1, 2031
• Study Completion (Estimated): January 1, 2035

Study Registration Dates

• First Submitted: November 23, 2025
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 6, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: cancer; obesity; endometrial cancer; Semaglutide; prehabilitation; hormonal therapy; prospective; minimally invasive surgery; robotic surgery; GLP-1 receptor agonist; early stage; endometrial hyperplasia; weight loss intervention; endometrial carcinoma; real-world evidence; levonorgestrel IUD; wegovy; metabolic optimization; ClinicalTrial
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Nutrition Disorders; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Overnutrition; Body Weight; Uterine Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Uterine Neoplasms; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Neoplasms; Overweight; Obesity; Endometrial Neoplasms; Endometrial Hyperplasia; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Health Care Quality, Access, and Evaluation; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Investigative Techniques; Epidemiologic Methods; Therapeutics; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Drug Therapy; Minimally Invasive Surgical Procedures; Pharmacologic Actions; Chemical Actions and Uses; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Physical Therapy Modalities; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Patient Care; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Diagnostic Techniques, Surgical; Endoscopy; Chemistry Techniques, Analytical; Spectrum Analysis; Epidemiologic Measurements; Pregnenediones; Pregnenes; Physical Conditioning, Human; Urogenital Surgical Procedures; Exercise; Gynecologic Surgical Procedures; Obstetric Surgical Procedures; Medroxyprogesterone; Hydroxyprogesterones; Progesterone; Megestrol; Diagnostic Techniques, Obstetrical and Gynecological; Hormone Replacement Therapy; Megestrol Acetate; Medroxyprogesterone Acetate; Progestins; Magnetic Resonance Spectroscopy; semaglutide; Resistance Training; Nutrition Assessment; Hysterectomy; Hysteroscopy; Estrogen Replacement Therapy
• Other Study ID Numbers: SHAPE-ENDO

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No