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

Summary

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.

Timeline

Start

2027-01

Primary completion

2031-04

Completion

2035-01

Publications

• Background 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.
• Background Iavazzo C, Gkegkes ID. Conservative management of patients with endometrial intraepithelial neoplasia (EIN): Factors that could affect response and pregnancy rates. Turk J Med Sci. 2022 Jun;52(3):870. doi: 10.55730/1300-0144.5384. Epub 2022 Jun 16. No abstract available.
• Background 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.
• Background Laurelli G, Falcone F, Gallo MS, Scala F, Losito S, Granata V, Cascella M, Greggi S. Long-Term Oncologic and Reproductive Outcomes in Young Women With Early Endometrial Cancer Conservatively Treated: A Prospective Study and Literature Update. Int J Gynecol Cancer. 2016 Nov;26(9):1650-1657. doi: 10.1097/IGC.0000000000000825.
• Background Fan Z, Li H, Hu R, Liu Y, Liu X, Gu L. Fertility-Preserving Treatment in Young Women With Grade 1 Presumed Stage IA Endometrial Adenocarcinoma: A Meta-Analysis. Int J Gynecol Cancer. 2018 Feb;28(2):385-393. doi: 10.1097/IGC.0000000000001164.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Rubino D, Abrahamsson N, Davies M, Hesse D, Greenway FL, Jensen C, Lingvay I, Mosenzon O, Rosenstock J, Rubio MA, Rudofsky G, Tadayon S, Wadden TA, Dicker D; STEP 4 Investigators. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1414-1425. doi: 10.1001/jama.2021.3224.
• Background Davies M, Faerch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021 Mar 13;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0. Epub 2021 Mar 2.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Minnella EM, Awasthi R, Loiselle SE, Agnihotram RV, Ferri LE, Carli F. Effect of Exercise and Nutrition Prehabilitation on Functional Capacity in Esophagogastric Cancer Surgery: A Randomized Clinical Trial. JAMA Surg. 2018 Dec 1;153(12):1081-1089. doi: 10.1001/jamasurg.2018.1645.
• Background Concin N, Matias-Guiu X, Vergote I, Cibula D, Mirza MR, Marnitz S, Ledermann J, Bosse T, Chargari C, Fagotti A, Fotopoulou C, Gonzalez Martin A, Lax S, Lorusso D, Marth C, Morice P, Nout RA, O'Donnell D, Querleu D, Raspollini MR, Sehouli J, Sturdza A, Taylor A, Westermann A, Wimberger P, Colombo N, Planchamp F, Creutzberg CL. ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma. Int J Gynecol Cancer. 2021 Jan;31(1):12-39. doi: 10.1136/ijgc-2020-002230. Epub 2020 Dec 18.
• Background 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.
• Background 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.

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