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Review
. 2025 Sep;35(9):101992.
doi: 10.1016/j.ijgc.2025.101992. Epub 2025 Jun 30.

Uterine leiomyosarcoma

Giorgio Bogani  1 , Giuseppe Caruso  2 , Isabelle Ray-Coquard  3 , Pedro T Ramirez  4 , Nicole Concin  5 , Natalie Yl Ngoi  6 , Robert L Coleman  7 , Andrea Mariani  8 , William Cliby  8 , Mario M Leitao Jr  9 , Nadeem Abu Rustum  10 , Paolo G Casali  1 , Alessandro Gronchi  1 , Ignace Vergote  11 , Judith Kroep  12 , Takayuki Enomoto  13 , Kazuhiro Takehara  14 , Hannelore Denys  15 , Masashi Takano  16 , Diane Provencher  17 , Pauline Wimberger  18 , Se Ik Kim  19 , Jae-Weon Kim  19 , Gian Franco Zannoni  20 , David Sp Tan  6 , Jvan Casarin  21 , Biagio Paolini  1 , Valentina Chiappa  1 , Francesco Raspagliesi  1 , Ilaria Cuccu  1 , Violante Di Donato  22 , David M O'Malley  23 , David Mutch  24 , Jubilee Brown  25 , Fernanda Herrera  26 , Nicoletta Colombo  27 , Sandro Pignata  28 , Giovanni Scambia  29 , Brian M Slomovitz  30 , Bradley J Monk  31
Affiliations
Review

Uterine leiomyosarcoma

Giorgio Bogani et al. Int J Gynecol Cancer. 2025 Sep.

Abstract

Uterine leiomyosarcoma is a rare and heterogeneous gynecological malignancy that poses a significant clinical challenge due to its aggressive nature and limited treatment options. Its multifactorial etiopathogenesis involves complex cytogenetic and molecular aberrations, including TP53, RB1, and chromothripsis-associated gene alterations. The non-specific clinical presentation, resembling other benign conditions, complicates early and accurate diagnosis, alongside intricate radiological and pathological patterns. Advanced imaging techniques, such as magnetic resonance imaging and computed tomography, are employed to differentiate uterine leiomyosarcoma from benign conditions, but no single test is definitive. For FIGO (International Federation of Gynecology and Obstetrics) stage I uterine leiomyosarcoma, treatment consists of en bloc total hysterectomy ± bilateral salpingo-oophorectomy. Patients with stage II to IV disease amenable to complete resection can undergo surgery followed by adjuvant systemic therapy and/or radiotherapy. Lymphadenectomy is unnecessary in patients lacking bulky nodes. Unresectable or unsuitable cases warrant primary systemic therapy and/or radiotherapy. Managing recurrent disease requires a multimodal approach tailored to factors such as the site and number of metastases, prior radiotherapy, and resectability. Multidisciplinary management and centralization in referral centers are crucial for individualized decision-making. Ongoing research explores the intricate cytogenetic and molecular aberrations of uterine leiomyosarcoma, paving the way for personalized treatment strategies. This review, developed following the European Society of Gynaecological Oncology/Gynecologic Cancer InterGroup/European Reference Network on Rare Adult Solid Cancers guidelines, explores the clinical presentation, diagnostic challenges, and evolving therapeutic strategies for uterine leiomyosarcoma, while also highlighting variations in clinical practice worldwide.

Keywords: Leiomyosarcoma; Smooth Muscle Tumor; Soft Tissue Sarcoma; Uterine Sarcoma.

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Conflict of interest statement

Declaration of Competing Interests GB: Novartis AG Pharma, Astellas, Italian Ministry of Health. IRC: Agenus, Blueprint, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, MacroGenics, Tesaro, and Clovis (honoraria); GSK, MSD, Roche, and BMS; consulting/advisory roles for AbbVie, Agenus, Advaxis, BMS, PharmaMar, Genmab, Pfizer, AstraZeneca, Roche/Genentech, GSK, MSD, Deciphera, Mersana, Merck Sereno, Novartis, Amgen, Tesaro and Clovis (honoraria to the institution); MSD, Roche and BMS, Novartis, AstraZeneca and Merck Sereno (research grant/funding); Roche, AstraZeneca, and GSK (travel support). PTR: given his role as Editor-in-Chief of the IJGC, PTR had no involvement in the peer review of this article and had no access to information regarding its peer review. NC: payments or honoraria for presentations from GSK, Seagen, Akesobio, AstraZeneca, eTheRNA immunotherapies NV, Kartos, MSD, Mersana, ImmunoGen, Eisai, Seattle Genetics, TouchIME, and Medscape Oncology; support for attending a meeting or travel from Roche, Genmab, and Amgen; payment for participation on a data safety monitoring board or advisory board from GSK, Mersana, Seagen, ImmunoGen, Akesobio, Eisai, AstraZeneca, Mersana, Seattle Genetics, eTheRNA immunotherapies NV, and Kartos; and leadership roles as President of ESGO and Chair of European Network for Gynaecological Oncological Trial groups Early Drug Development Network. RLC: grants or contracts from AstraZeneca, Clovis Oncology, Genelux, Genmab, Merck, ImmunoGen, and Roche/Genentech; consulting fees from AbbVie, Agenus, Alkermes, AstraZeneca, Clovis Oncology, Deciphera, Genelux, Genmab, GSK, ImmunoGen, Novocure, Merck, OncoQuest, Onxerna, Regeneron, and Roche/Genentech; honoraria from AstraZeneca, Clovis Oncology, Merck, and Roche/Genentech; and participation on data safety monitoring or advisory boards for Eisai/BMS and VBL Therapeutics. MML: Honorary Intuitive Surgical; Consulting Medtronic and Ethicon. NAR: research funding paid to the institution from GRAIL. PGC: has reported Institution research grants from Advenchen Laboratories, Amgen Dompé, AROG Pharmaceuticals, Bayer, Blueprint Medicines, Boehringer Ingelheim, Daiichi Sankyo, Deciphera, Eisai, Eli Lilly, Epizyme Inc, Foghorn Ther Inc, Glaxo, Hutchinson MediPharma Ltd, Inhibrx Inc, Karyopharm Pharmaceuticals, PTC Ther, Novartis, Pfizer, PharmaMar, Rain Oncology, and SpringWorks Ther. AG: funding to the institution from PharmaMar and Nanobiotix; consulting fees from Novartis, Pfizer, Bayer, Lilly, PharmaMar, SpringWorks, and Boehringer Ingelheim; honoraria for presentations from PharmaMar and Deciphera; travel support from PharmaMar; and leadership roles as the International Representative on the Executive Council of the Society of Surgical Oncology, a member of the Board of Directors of the European Society of Surgical Oncology, and a member of the Board of Directors of the Italian Sarcoma Group. IV: Consulting Advice: Akesobio, Bristol-Myers Squibb, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffmann-La Roche, Genmab, GSK, ITM, Jazzpharma, Karyopharm, MSD, Novocure, Oncoinvent, Sanofi, Regeneron, Seagen, Sotio, Zentalis. Consulting Data monitoring Committees: Agenus, AstraZeneca, Corcept, Daiichi, F. Hoffmann-La Roche, Immunogen, Kronos Bio, Mersana, Novartis, OncXerna, Verastem Oncology. TE: lecture fee from AstraZeneca, MSD, Kaken Pharmaceutical Company, and Chugai. KT: funding/fee from Takeda, AstraZeneca, EISAI, Chugai Pharma, MSD, Sanofi. HD: Consulting or Advisory Role: Roche (Inst), PharmaMar (Inst), AstraZeneca (Inst), Eli Lilly (Inst), Novartis (Inst), Amgen (Inst), GSK (Inst), Seagen (Inst), MSD (Inst), Gilead (Inst), AbbVie (Inst), Esai (Inst); Travel, Accommodations, Expenses: Teva (Inst), AstraZeneca (Inst), MSD (Inst), Gilead (Inst), GSK (Inst), Novartis (Inst), Eli Lilly (Inst). DP: institutional research funding from Exactis Innovation and consulting fees and advisory board participation from AstraZeneca plc, Merck & Co Inc, and GlaxoSmithKline plc. PW: research funding from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, Lilly, honoraria from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, Daichii Sankyo. PW participates in advisory boards from Amgen, AstraZeneca, MSD, GlaxoSmithKline, Novartis, Pfizer, Roche Pharma, Clovis, TEVA, Eisai, Lilly, Gilead, and Daichii Sankyo. DSPT: grants from the Singapore Ministry of Health’s National Medical Research Council Clinician Scientist award and Pangestu Family Foundation Gynaecological Cancer Research Fund. Fees for advisory board and consultancy roles from AstraZeneca, Roche, MSD, Merck Serono, GSK, and Eisai for a presentation. Research funding AstraZeneca, Roche, Bayer, BMS, MSD, Eisai, and Karyopharm. Stock ownership in the Asian Microbiome Library (AMiLi). DOM: grants from Ajinomoto, BMS, Cerulean Pharma, GOG Foundation, INC Research, InVentiv Health Clinical, Iovance Biotherapeutics, Ludwig Cancer Research, New Mexico Cancer Care Alliance, PRA International, Serono, Stemcentrx, Tracon Pharmaceuticals, and Yale University; has been a consultant/advisory board member for AbbVie, Ambry, Amgen, Array Biopharma, Clovis Oncology, EMD Serono, Ergomed, Janssen/Johnson & Johnson, Myriad Genetics, Novocure, Regeneron, Tarveda, and VentiRx; was a member of a steering committee for Genentech/Roche and Merck; and received personal fees from Agenus, Eisai, GSK and ImmunoGen. JB: honoraria from Olympus; consulting or advisory role at Caris, GlaxoSmithKline, Clovis, AstraZeneca, and Genentech; and speakers’ bureau at Clovis. FH: Accuray inc, Bioprotect, Bristol-Myers Squibb, Roche-ImFlame/ImCore, Nanobiotix, AstraZeneca, Eisai, MSD, Seagen, Prostate Cancer Foundation, San Salvatore Foundation, Lundin Foundation (grant research support); Johnson & Johnson, Boehringer Ingelheim, Seagen, MSD, Bristol-Myers Squibb, AstraZeneca, Eisai (Consultant, honoraria, travel expenses); EORTC chairman Gynecology Cancer Group, ESMO Scientific Committee member for drug development, ASTRO Scientific Committee Annual Meeting, ESTRO Scientific Committee Annual Meeting (Academic collaborations and advisory). NC: AstraZeneca, Clovis Oncology, Inc, EISAI, GlaxoSmithKline, LLC., Immunogen, Merck, MSD, Mersana Therapeutics, Nuvation, Onxerna, Pieris, Gilead, Biontech, Genmab (Consultant, honoraria and/or SAB); ACTO (Leadership role). SP: research funding from Roche, MSD, GSK, Pfizer, and AstraZeneca; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing, or educational events from AstraZeneca, MSD, Roche, Pfizer, Novartis, and GSK; and participation on a Data Safety Monitoring Board or Advisory Board for GSK, MSD, Eisai, Biontech, and AstraZeneca. GS: AstraZeneca, Merck Sharp & Dohme, Covidien AG, Tesaro Bio Italy S.r.l, and Johnson & Johnson (consulting/advisory role); Olympus Europa SE & CO, GlaxoSmithKline S.p.A, Baxter Healthcare SA, and Intuitive Surgical Inc (honoraria). BMS: AbbVie, AstraZeneca, Eisai, Genentech, Genmab, GlaxoSmithKline, LLC, GOG Foundation, Incyte, Karyopharm, Merck, Novartis, Pfizer, Regeneron, Verastem, Zentalis. BJM: AbbVie, Acrivon, Adaptimmune, Agenus Inc, Akeso Biopharma, Amgen Inc, Aravive Inc, AstraZeneca, Bayer, Clovis Oncology, Inc, EISAI, Elevar Therapeutics, EMD Serono, Inc, Genentech, Genmab/Seattle Genetics, GlaxoSmithKline, LLC., GOG Foundation, Gradalis, Inc, Heng Rui, Immunogen, Incyte Corporation, Iovance Biotherapeutics, Janssen Biotech, Karyopharm Therapeutics Inc, Laekna, Macrogenics, Merck, Myriad Genetic Laboratories, Inc, Mersana Therapeutics, Novartis, Novocure Inc, OncoC4, Panavance, Pzer Inc, Pzer International LLC, Pieris, Puma Biotechnology, Inc, Regeneron Pharmaceuticals, Inc, Sorrento Therapeutics, Takeda Development Center Americas, Inc, US Oncology, VBL, Verastem, Inc, Zentalis (Consultant, honoraria and/or SAB); HonorHealth Research Institute (Director/principal investigator). The other authors have nothing to disclose.

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