This chapter should be cited as follows:
Puglisi S, Fick F, et al., Glob Libr Women's Med
ISSN: 1756-2228; DOI 10.3843/GLOWM.422083

The Continuous Textbook of Women’s Medicine Series – Gynecology Module

Volume 13

Gynecological cancer

Volume Editors: Professor Hextan Ngan, Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong
Professor Karen Chan, Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong

Chapter

Management of Uterine Sarcoma

First published: May 2026

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INTRODUCTION

Uterine sarcomas are a heterogeneous group of malignant uterine tumors of mesenchymal origin. They are rare, accounting for less than 5% of all uterine malignancies. The main histological subtypes include uterine leiomyosarcoma (uLMS), endometrial stromal sarcoma (ESS) – subdivided into low-grade (LG-ESS) and high-grade (HG-ESS) variants – adenosarcoma, undifferentiated uterine sarcoma (UUS), and several very rare entities such as perivascular epithelioid cell tumors (PEComas) and NTRK-rearranged sarcomas.¹ These tumors typically occur between the fourth and sixth decades of life and are characterized by aggressive clinical behavior with a high risk of local recurrence and distant metastasis, even in early stages. Prognosis remains poor, particularly for patients with high-grade subtypes.

Accurate diagnosis of uterine sarcomas is challenging due to their rarity and morphological overlap with benign uterine lesions such as leiomyomas or smooth muscle tumors of uncertain malignant potential (STUMP). Histopathological evaluation integrated with immunohistochemical and molecular analyses is essential for establishing the diagnosis and guiding therapy. Recent ESGO/EURACAN/GCIG consensus guidelines emphasize that diagnostic confirmation should be performed by experienced gynecologic pathologists at specialized sarcoma referral centers, in which advanced molecular testing – including RNA sequencing for fusion detection (e.g. BCOR, YWHAE, JAZF1 rearrangements) – is routinely available. This multidisciplinary diagnostic approach ensures appropriate classification, enables identification of actionable molecular targets and supports personalized management strategies.¹

Given their biological diversity and clinical complexity, uterine sarcomas require individualized, evidence-based management within specialized multidisciplinary teams. The ESGO/EURACAN/GCIG 2024 guidelines advocate for centralized care, expert imaging and pathology assessment, and tailored therapeutic approaches based on histological subtype, disease stage and molecular profile. Despite progress in understanding these tumors, unmet needs persist regarding early diagnosis, clinical differentiation from benign myomas, systemic treatment efficacy and long-term survivorship outcomes, highlighting the importance of continued international collaboration and research in this rare but challenging group of malignancies.

Although recent guidelines have standardized the diagnostic and therapeutic approach to uterine sarcomas, real-world management often remains inconsistent due to limited expertise, variability in access to molecular testing, and differences in institutional resources. Moreover, therapeutic options for advanced or recurrent disease remain suboptimal, and prognostic biomarkers are still evolving. Therefore, further studies addressing optimal diagnostic pathways, treatment sequencing, and the integration of molecularly guided therapies are crucial to improving outcomes in patients with uterine sarcoma.

In this chapter we provide an overview of the management of uterine sarcoma.

CLINICAL PRESENTATION AND DIAGNOSTICS

Uterine sarcomas exhibit a highly heterogeneous and often non-specific clinical presentation, reflecting their different histological subtypes, each associated with distinct biological behavior and degrees of aggressiveness.² Common presenting symptoms include abnormal vaginal bleeding, a palpable or rapidly enlarging pelvic mass, and pelvic or abdominal pain. Some patients report a sensation of pelvic pressure, fullness in the abdomen, or, less frequently, symptoms related to urinary or gastrointestinal compression.³ Occasionally, the presenting manifestations are related to tumor rupture (hemoperitoneum), extrauterine extension (one-third to one-half of cases) or metastases.⁴ The first approach to diagnosis is usually a pelvic ultrasound followed by pelvic magnetic resonance imaging (MRI).⁵ MRI should be done by specialized radiologists.

Because presenting symptoms overlap significantly with those of benign conditions, such as leiomyomas, preoperative distinction is challenging; a substantial proportion of cases are initially misdiagnosed as fibroids and are recognized as sarcoma only following surgical intervention or histopathological examination. Larger tumor size, heterogeneous echotexture, central necrosis and marked hypervascularity on imaging may aid differential diagnosis but are not specific.⁶ An algorithm has been developed to distinguish malignant uterine sarcomas from atypical leiomyomas using four MRI features, including lymphadenopathy or peritoneal implants, T2 signal characteristics, diffusion-weighted imaging signal intensity, and apparent diffusion coefficient values. The algorithm categorizes uterine masses into three groups: highly suspicious, probably benign and certainly benign. Prospective validation is required before it can be incorporated into routine clinical practice.⁷ The use of artificial intelligence (machine learning) to optimize preoperative diagnostic algorithms is beginning to be implemented.^8,9

There are no dedicated blood-based tumor markers for this disease. An endometrial or transvaginal biopsy may be performed to try to establish a histological diagnosis, but these approaches have limited sensitivity. In many cases, the diagnosis is ultimately confirmed only after examining the surgical specimen.¹⁰ Transabdominal biopsy and morcellation are generally avoided because they may increase the risk of spreading the disease within the peritoneal cavity.¹¹ Richtárová et al. showed that transabdominal biopsy for preoperative evaluation of sonographically atypical myometrial lesions in patients scheduled for uterine surgery is safe and accurate, although the majority of patients were diagnosed with benign disease and not uterine sarcoma.¹²

From a pathological-diagnosis standpoint, immunohistochemistry is essential to support tumor identification and guide therapeutic decisions. In addition to immunohistochemistry, molecular testing for fusion transcripts or mutations has become indispensable for refining tumor classification and identifying actionable therapeutic targets. These analyses can be performed on both biopsy and resection specimens.¹³ In cases of suspected uterine sarcoma, the patient should be referred to a specialized center with dedicated expertise, including experienced pathologists and radiologists.¹⁴

Pathological and molecular features

Uterine mesenchymal tumors (UMTs) represent a broad and heterogeneous category of non-epithelial neoplasms with different degrees of aggressiveness. They are the second most frequent tumors of the uterine corpus after endometrial carcinoma, making up roughly 8% of all uterine corpus malignancies.¹⁵ The 2020 WHO classification groups uterine sarcomas into the following categories: smooth muscle tumors, including STUMP and leiomyosarcomas; endometrial stromal tumors (low grade and high grade); undifferentiated uterine sarcoma; uterine tumor resembling ovarian sex cord tumor (UTROSCT); PEComa; inflammatory myofibroblastic tumor (IMT); and adenosarcoma.¹⁶ Uterine carcinosarcoma is currently regarded as a metaplastic carcinoma rather than a true sarcoma but shares overlapping biology.¹⁷ Recent series also recognize emerging molecularly defined entities such as NTRK-rearranged spindle cell tumors and SMARC-deficient uterine sarcomas, further broadening the histologic spectrum.¹ In addition, certain forms of uterine sarcoma may be associated with genetic predisposition syndromes, among which uterine rhabdomyosarcoma is associated with DICER1 syndrome.¹⁸ From a histological standpoint, uterine leiomyosarcoma is a malignant smooth-muscle neoplasm, defined by three key histopathologic features: moderate-to-severe cytologic atypia, tumor cell necrosis and a mitotic rate of ≥10 per 10 high-power fields (HPFs). A definitive diagnosis requires the presence of at least two of these criteria.¹⁹ Three main subtypes have been described: spindle, epithelioid and myxoid leiomyosarcoma. Immunohistochemically, these tumors express smooth-muscle markers such as smooth-muscle actin, desmin and h-caldesmon, with frequent overexpression of p16 and aberrant p53 and a high Ki-67 index, findings that can assist in distinguishing leiomyosarcoma from atypical leiomyoma and STUMP.²⁰ At the genomic level, leiomyosarcomas represent complex-genomic sarcomas, with numerous copy-number alterations and mutations affecting cell-cycle and DNA-damage response pathways rather than a single pathognomonic translocation. Recurrent alterations have been reported in TP53, RB1, ATRX and genes involved in homologous recombination and DNA repair, changes that may have prognostic implications and could inform eligibility for biomarker-driven clinical trials.²¹ 

LG-ESS is a malignant stromal tumor resembling proliferative-phase endometrial stroma, typically showing infiltrative growth into the myometrium and sometimes lymphovascular invasion.²² Microscopically, it consists of uniform spindle-to-oval cells with minimal atypia, low mitotic activity and a delicate vascular network. Variant features can include smooth muscle, fibromyxoid or sex cord-like differentiation.²³ Immunohistochemically, LG-ESS shows strong, diffuse expression of CD10, estrogen receptor (ER) and progesterone receptor (PR), and variable expression of cyclin D1. Smooth muscle markers (desmin, h-caldesmon) highlight areas of smooth muscle differentiation and sex-cord-like elements may express inhibin, calretinin, melan-A, WT1 and CD99.²⁴ Molecular analysis can aid diagnosis, as approximately two-thirds of LG-ESS harbor gene fusions involving polycomb group genes, most commonly JAZF1–SUZ12, followed by JAZF1–PHF1, EPC1–PHF1 and MEAF6–PHF1. Less common fusions include MBTD1–EZHIP, BRD8–PHF1, EPC2–PHF1 and EPC1–SUZ12.²² Rarely, LG-ESS with these rearrangements can undergo transformation to high-grade sarcoma, associated with increased mitotic activity, nuclear enlargement and more aggressive clinical behavior.²⁵ 

HG-ESS is an aggressive stromal malignancy composed of uniformly high-grade round or spindle-shaped cells, occasionally mixed with areas resembling LG-ESS. The tumor may grow in an expansive, infiltrative or permeative manner, often showing more than one invasion pattern. Marked lymphovascular invasion, high mitotic activity and tumor necrosis are common features.²⁶ HG-ESS encompasses several molecular subtypes identifiable by FISH or sequencing: YWHAE–NUTM2–rearranged tumors that show high-grade round morphology and typically express cyclin D1, BCOR, KIT, CD56 and CD99;²⁷ ZC3H7B–BCOR–fusion tumors which are cyclin D1–positive with variable BCOR and ER/PR expression, usually CD10-positive and may show focal smooth-muscle marker expression; BCOR-ITD tumors that show stronger cyclin D1/BCOR expression and typically lack ER/PR;²⁸ and HG-ESS NOS which describes high-grade tumors with a low-grade stromal component but without a defining genetic alteration.²⁹

UUS is a high-grade mesenchymal tumor with no specific differentiation, diagnosed by exclusion. It shows destructive myometrial invasion, marked cytologic atypia, high mitotic activity and frequent necrosis/lymphovascular space invasion (LVSI). Tumors often abnormally express p53 and p16, with variable expression of ER, PR and CD10.²² Molecular testing is required to exclude other defined high-grade stromal sarcomas with YWHAE, JAZF1 or NTRK rearrangements.³⁰

An overview of the different subtypes of uterine sarcomas is given in Table 1.

Prognostic factors

Prognosis is strongly influenced by tumor biology, stage at presentation and adequacy of surgical treatment. The histological subtype is one of the most important determinants of outcome: LMS and HG-ESS generally have the worst prognosis while LG-ESS typically follows an indolent course.¹⁶ Stage at diagnosis is a key prognostic factor. Patients with disease confined to the uterus have markedly better survival, while extrauterine spread is associated with high recurrence rates.³¹ Tumor size, mitotic index and the presence of necrosis further stratify risk, especially in LMS. LVSI is consistently associated with early dissemination and worse outcomes across histotypes.⁴ Complete, non-morcellated removal of the tumor is essential, as morcellation or fragmentation significantly increases the risk of peritoneal dissemination.³²

THERAPEUTIC MANAGEMENT

Surgery

Surgery remains the cornerstone of management and the only potentially curative modality for uterine sarcomas. Complete surgical resection with negative margins (R0 resection) is the primary therapeutic goal across all histological subtypes. 

Total hysterectomy is the standard treatment for disease confined to the uterus (FIGO stages I–II) and should be performed with careful attention to maintaining uterine integrity. Morcellation or any form of intraperitoneal fragmentation should be strictly avoided, as these procedures are associated with increased risk of peritoneal dissemination and worse survival outcomes.^1,14

Total hysterectomy with bilateral salpingo-oophorectomy represents the standard surgical approach for uterine sarcomas, including uLMS, in postmenopausal women, primarily for staging purposes rather than for hormonal ablation. In uLMS, ovarian metastases are uncommon and the tumor is rarely estrogen-dependent; therefore, ovarian preservation may be considered in carefully selected premenopausal patients after individualized discussion of risks and benefits. In contrast, in LG-ESS and other estrogen-receptor-positive uterine sarcomas, bilateral salpingo-oophorectomy is generally recommended, as ovarian preservation has been associated with a higher risk of recurrence, although without a demonstrated impact on overall survival.^33,34,35 Therefore, the ESGO guideline recommends a carefully weighed benefit–risk evaluation of ovarian preservation in young patients when the ovaries are uninvolved. Systematic pelvic and para-aortic lymphadenectomy is not routinely indicated because nodal metastases are uncommon and nodal dissection does not improve overall survival.²² However, enlarged or suspicious lymph nodes should be resected for staging or symptom control purposes.

In advanced (FIGO stages III–IV) or recurrent disease, cytoreductive surgery with maximal tumor debulking should be performed when complete macroscopic resection appears feasible. The completeness of cytoreduction is a major prognostic determinant.

Such procedures should be undertaken only in high-volume sarcoma or gynecologic oncology centers, in which multidisciplinary tumor boards guide the sequencing of surgery, systemic therapy and follow-up care,^1,36 and in which open abdominal surgery (laparotomy) is performed by experienced surgeons.

Systemic treatment

Systemic therapy plays an essential role in the management of advanced, recurrent or metastatic uterine sarcomas and is guided by histologic subtype and molecular profile. 

For localized uterine leiomyosarcoma, there is no randomized evidence but indirect data suggest that (neo-)adjuvant treatment may be beneficial.^1,37,38,39 The ESGO guideline recommends inclusion in ongoing clinical trials to further evaluate its potential benefit. Systemic endocrine therapy might be considered in LG-ESS Stage I with intraoperative morcellation and in LG-ESS Stage II (or higher).

In patients with HG-ESS, adjuvant systemic therapy is not standard for FIGO stage-I disease. However, postoperative chemotherapy may be considered in patients with FIGO stage-I–III disease who are at high risk of relapse, following informed discussion and shared decision-making. In cases of morcellation of HG-ESS or undifferentiated uterine sarcoma, adjuvant chemotherapy should be considered because of the substantially increased risk of recurrence.¹

Uterine leiomyosarcoma (uLMS)

For metastatic or unresectable uLMS, first-line systemic therapy includes the combination of doxorubicin and trabectedin, based on the results of the Phase-III LMS-04 trial, which demonstrated a significant progression-free survival benefit with manageable toxicity compared with doxorubicin alone.⁴⁰ Combination therapy with gemcitabine and docetaxel is frequently used as an alternative in first- or second-line settings, showing response rates of approximately 25–35%.⁴¹ In pretreated patients with doxorubicin alone, trabectedin and pazopanib have demonstrated clinical benefit, with improved progression-free survival compared to placebo.^42,43 Eribulin is another option for patients with advanced or refractory disease, showing non-inferiority to dacarbazine in Phase-III trials.⁴⁴

Endometrial stromal sarcoma (ESS)

LG-ESS is typically hormone receptor-positive and indolent and endocrine therapy represents the mainstay of systemic treatment. Aromatase inhibitors (letrozole, anastrozole) and progestins (megestrol acetate, medroxyprogesterone acetate) are effective options for recurrent or metastatic disease, while tamoxifen and estrogen replacement therapy are contraindicated.^45,46

In contrast, HG-ESS and UUS display more aggressive behavior and are treated according to soft-tissue sarcoma protocols. First-line systemic therapy options include doxorubicin (if not previously administered in the adjuvant setting), either in combination with ifosfamide or as a single agent. For patients who are not candidates for doxorubicin, gemcitabine plus docetaxel is an alternative.^1,47 In the relapsed or metastatic setting, systemic treatment options include continuous infusion of high-dose ifosfamide, gemcitabine plus docetaxel, or single-agent pazopanib or trabectedin.^43,48

Molecular profiling may reveal characteristic alterations, such as BCOR, BCORL1 or YWHAE fusions, which can guide the use of experimental or targeted therapies.^1,49

Other rare subtypes

PEComas harboring TSC1 or TSC2 mutations can respond favorably to mTOR inhibitors (sirolimus, everolimus, temsirolimus),⁵⁰ while NTRK-rearranged sarcomas are sensitive to NTRK inhibitors such as larotrectinib and entrectinib.⁵¹ These molecularly guided options exemplify the increasing role of precision medicine in uterine sarcoma management.

Additional treatment options

Radiotherapy

The role of radiotherapy in uterine sarcoma is limited and largely palliative. Adjuvant pelvic radiotherapy may be considered in selected high-risk cases (e.g. close or positive surgical margins, pelvic recurrence) to improve local control but has not demonstrated a significant survival benefit.^52,53,54,55 For isolated metastases or oligometastatic disease, stereotactic body radiotherapy (SBRT) and other local ablative approaches can provide durable control in selected patients with limited disease burden.⁵⁶ In cases of vaginal hemorrhage, radiotherapy can be performed to stop bleeding.⁵⁷

Targeted therapy

Endocrine therapy remains central to the treatment of LG-ESS, either as primary therapy for advanced disease or as maintenance after resection. The targeted agent, pazopanib, an oral multikinase inhibitor, is approved for pretreated soft-tissue sarcomas and provides modest benefit in progression-free survival.⁴³ For selected molecular subtypes, therapies targeting specific genetic alterations, such as CDK4/6 inhibitors in hormone receptor-positive sarcomas, mTOR inhibitors for TSC-mutated PEComas or immune checkpoint inhibitors in tumors with mismatch repair deficiency, represent emerging strategies under investigation.^{1,51,58,59,60}

Follow-up and survivorship

Post-treatment surveillance should be individualized based on histological subtype and risk of recurrence. Clinical evaluation and imaging (CT or MRI) are recommended every 3–6 months during the first 3 years, every 6–12 months for the following 2 years and annually thereafter, as late recurrences can occur.¹ Survivorship care should address the long-term effects of systemic therapy, hormonal deprivation and psychosocial wellbeing, particularly in younger women undergoing surgical menopause.

Risk of recurrence

The risk of recurrence in uterine sarcomas remains high, with approximately 40–70% of patients experiencing relapse within 10 years of diagnosis, depending on histological subtype, tumor grade and completeness of surgical resection.^{1,61,14,46,62}

Overall survival declines markedly over time, with reported rates of approximately 75% at 2 years, 55–60% at 5 years and 35–40% at 10 years, underscoring the poor long-term prognosis particularly for high-grade and advanced-stage tumors.^1,61,63,41 In this heterogeneous group of uterine sarcomas, different risk classifications are established. For PEComas, the modified Folpe classification was found to be the most accurate in predicting tumor behavior.⁶⁴

FUTURE

Recent research has shed light on crucial genetic mutations in uterine sarcomas that are pivotal for developing targeted therapies.⁶⁵

In LG-ESS, the frequent JAZF1–SUZ12 fusion disrupts the PRC2 complex, causing loss of normal epigenetic control and activation of pathways such as Wnt signaling. This leads to abnormal expression of genes involved in cell growth, adhesion and immune response. Other, rarer fusions often affect the same PRC2 components, suggesting a shared downstream mechanism. These molecular alterations not only aid diagnosis but also highlight the Wnt pathway as a promising therapeutic target.⁶⁶ HG-ESS is driven by the YWHAE–NUTM2 fusion, which produces the oncogenic 14–3-3 protein and activates RAF/MEK/MAPK and Hippo/YAP-TAZ pathways.⁶⁷ Silencing this fusion reduces MAPK signaling and cyclin D1 expression, leading to impaired proliferation.⁶⁸ Cyclin D1 knockdown further causes RB1 dephosphorylation and tumor growth inhibition.⁶⁶ MEK and CDK4/6 inhibitors show strong, synergistic antiproliferative activity, highlighting promising therapeutic targets.⁶⁰ Similarly, BCOR-rearranged ESS commonly display MDM2 amplification and activation of the cyclin D1–CDK4 axis, closely resembling other CDK4/6-inhibitor responsive sarcomas. This supports CDK4/6 blockade, alone or combined with MDM2 inhibitors, as a promising therapeutic strategy for BCOR-fusion positive tumors.⁶⁹

Gene expression studies in HG-ESS with YWHAE or BCOR fusions/ITD show upregulation of NTRK3, FGFR3 and RET, supporting potential use of TKIs like pazopanib or imatinib. Increased GLI1 and PTCH1 expression also suggests a role for Sonic Hedgehog pathway inhibitors.⁷⁰ Additional alterations include c-KIT mutations, PDGFR abnormalities and Wnt pathway dysregulation, all representing actionable targets. Clinical reports document responses to pazopanib in YWHAE-rearranged, c-KIT–high tumors and to imatinib in c-KIT–positive ESS.⁷¹ A newly described aggressive HG-ESS subtype shows ERBB2/ERBB3 mutations and S100/SOX10 positivity, though its classification and therapeutic implications remain under investigation.⁷² Immunotherapy is emerging as a promising option for ESS, especially HG-ESS, which often shows immune pathway activation, variable PD-L1 expression and fusion proteins that may act as neoantigens. Some ESS subtypes, including SMARCA4-deficient tumors, display high immune infiltration and could benefit from checkpoint inhibitors or other immune-based strategies.⁷³ Although clinical evidence is still limited, integrating immune markers and genomic profiling may help identify patients most likely to respond to immunotherapy.⁷⁴ Finally, in uLMS, somatic BRCA2 mutations can cause homologous recombination deficiency, indicating a potential but still experimental sensitivity to PARP inhibitors. Early studies suggest that combination therapies targeting DNA repair, such as temozolomide plus olaparib, may be effective in tumors with BRCA or TP53 alterations. However, in an open-label, single-center, single-arm, Phase-II study by Movva et al. (n = 20), the addition of rucaparib to nivolumab in patients with advanced refractory LMS did not improve the efficacy of immune checkpoint inhibitors. Adverse events, especially due to overlapping toxicities, were frequent and often led to dose delays and modifications.⁷⁵

Although these strategies remain investigational, they represent a promising avenue to complement conventional chemotherapy in aggressive uterine sarcomas.⁷⁶

CONCLUSION

Uterine sarcomas remain among the most challenging malignancies in gynecologic oncology due to their rarity, histological heterogeneity and often aggressive biological behavior. Despite recent progress in understanding their molecular underpinnings and the publication of comprehensive international guidelines, outcomes remain unsatisfactory, particularly for high-grade and advanced-stage disease. The median overall survival for patients with metastatic uLMS rarely exceeds 3 years and recurrence rates remain high across all histological subtypes.^1,61

Accurate histopathological and molecular diagnosis is a critical determinant of appropriate management. The ESGO/EURACAN/GCIG 2024 consensus guidelines emphasize the need for expert pathological review, centralization of care and molecular profiling to distinguish between subtypes with overlapping morphology, such as LG-ESS, HG-ESS or STUMP.¹

The large European population-based study by Ray-Coquard et al. demonstrated that over 40% of initial sarcoma diagnoses were modified following centralized expert review, often resulting in changes to patient management.¹⁴ These findings underscore that multidisciplinary decision-making in specialized sarcoma centers is essential to ensure diagnostic accuracy and optimal treatment planning. In particular, the primary radiological diagnostics are crucial for the staging and right treatment decisions.

Surgery remains the cornerstone of therapy and the only curative option in early-stage disease. The avoidance of uterine morcellation has become a crucial principle, as intraoperative dissemination is associated with poorer survival outcomes.^1,77 Complete resection with negative margins (R0) is the most significant prognostic factor across all subtypes, whereas the role of lymphadenectomy is limited to staging or debulking visibly enlarged nodes. For advanced or recurrent disease, aggressive cytoreductive surgery in experienced centers can improve local control and survival, particularly when combined with systemic therapy.²

Systemic treatment continues to evolve, but effective options remain limited. Doxorubicin-based regimens in combination with trabectedin remain standard first-line therapy for uLMS and high-grade sarcomas, while gemcitabine–docetaxel, trabectedin and pazopanib are key agents in later lines.^41,42,43 For LG-ESS, endocrine therapy has become the preferred systemic option, achieving durable responses with minimal toxicity^50,78 but with contraindication for tamoxifen. The increasing integration of molecular testing is reshaping the therapeutic landscape by characterizing the tumors more individually and therefore giving the possibility to treat more specifically.

mTOR inhibitors have shown activity in TSC-mutated PEComas⁵⁰ and NTRK inhibitors provide remarkable efficacy in fusion-driven tumors.⁵¹ These developments mark an important step toward precision oncology in uterine sarcomas, although access to targeted therapy and molecular diagnostics remains inconsistent globally.

The role of radiotherapy remains largely supportive: adjuvant pelvic irradiation may reduce local recurrence without improving survival,^54,55 while stereotactic body radiotherapy can provide durable control in selected oligometastatic cases.⁵⁶ Overall, optimal integration of radiation, in the context of surgery and systemic therapy requires individualized, multidisciplinary planning based on histology, stage and patient factors.

Despite these advances, major unmet needs persist. The rarity of uterine sarcomas limits the feasibility of large randomized trials, resulting in most evidence being derived from small cohorts and retrospective analyses. Furthermore, quality-of-life outcomes, survivorship issues and fertility preservation strategies remain underrepresented in current research. Establishing international registries and collaborative studies, such as those supported by EURACAN and GCIG, is crucial to generate high-quality data, evaluate novel systemic therapies and refine prognostic biomarkers.

In conclusion, the management of uterine sarcomas, as rare but very aggressive uterine cancer with poor prognosis, requires a coordinated, multidisciplinary approach grounded in accurate diagnosis, specialized surgical expertise and personalized systemic therapy. Ongoing translational research, molecular profiling and international collaboration will be pivotal in improving outcomes and developing more effective, biology-driven treatment strategies for this kind of tumor.

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