Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021)

Abstract

Purpose This is an official guideline, published and coordinated by the Germany Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe, DGGG). Because of their rarity and heterogeneous histopathology, uterine sarcomas are challenging in terms of their clinical management and therefore require a multidisciplinary approach. To our knowledge, there are currently no binding evidence-based recommendations for the appropriate management of this heterogeneous group of tumors.

Methods This S2k guideline was first published in 2015. The update published here is once again the result of the consensus of a representative interdisciplinary committee of experts who were commissioned by the Guidelines Committee of the DGGG to carry out a systematic search of the literature on uterine sarcomas. Members of the participating professional societies achieved a formal consensus after a structured consensus process.

Recommendations 1.1 Epidemiology, classification, staging of uterine sarcomas. 1.2 Symptoms, general diagnostic workup, general pathology or genetic predisposition to uterine sarcomas. 2. Management of leiomyosarcomas. 3. Management of low-grade endometrial stromal sarcomas. 4. Management of high-grade endometrial stromal sarcoma and undifferentiated uterine sarcomas. 5. Management of adenosarcomas. 6. Rhabdomyosarcomas of the uterus in children and adolescents. 7. Follow-up of uterine sarcomas. 8. Management of morcellated uterine sarcomas. 9. Information provided to patients.

I  Guideline information

Guidelines program of the DGGG, OEGGG and SGGG

For information on the guidelines program, please refer to the end of the guideline.

Citation format

Sarcoma of the Uterus. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/074, April 2021). Geburtsh Frauenheilk 2022; 82: 1337–1367

Guideline documents

The complete long version in German and a slide version of this guideline together with a list of the conflicts of interest of all of the authors are available on the homepage of the AWMF: http://www.awmf.org/leitlinien/detail/ll/015-072.html

Guideline authors

See Tables 1 and 2 .

Tab. 1  Lead author and/or coordinating author of the guideline.

Author	AWMF professional society
Prof. Dominik Denschlag	German Society for Gynecology and Obstetrics (Deutsche Gesellschaft für Gynäkologie und Geburtshilfe)

Tab. 2  Participating guideline authors.

Author Mandate holder	DGGG working group (AG)/ AWMF/non-AWMF professional society/organization/association
Prof. Dr. E. Petru	ÖGGG
Prof. Dr. M. Fehr	SGGG
Prof. Dr. M. Beckmann	DGGG
PD Dr. S. Ackermann, Prof. Dr. P. Harter, Prof. Dr. P. Mallmann, PD Dr. F. Thiel, Prof. Dr. M. Wallwiener	AGO of the DGGG/DKG
Prof. Dr. A. Mustea	NOGGO
Prof. Dr. U. Ulrich, PD Dr. I. Juhasz-Boess	AGE
Prof. Dr. D. Schmidt	DGP/AOP
Prof. Dr. L.-C. Horn	BDP and DGP (representative of Prof. Schmidt)
PD Dr. P. Reichardt	DGHO
Prof. Dr. D. Vordermark	DEGRO
Prof. Dr. K. Lindel	ARO
Prof. Dr. T. Vogl	DRG
Prof. Dr. T. Kröncke	DEGIR
Dr. W. Cremer (Hamburg)	BVF
PD Dr. K. Kast	AET
Prof. Dr. G. Egerer, Dr. R. Mayer-Steinacker	AGSMO
Heidemarie Haase	Federal Association of Womenʼs Self-help After Cancer (Bundesverband Frauenselbsthilfe nach Krebs e. V.)
PD Dr. S. Hettmer	Society for Pediatric Oncology and Hematology (Gesellschaft für Pädiatrische Onkologie und Hämatologie)

The following professional societies/working groups/organizations/associations stated that they wished to contribute to the guideline text and participate in the consensus conference and nominated representatives to contribute and attend ( Table 2 ).

II  Guideline Application

Purpose and objectives

The purpose of this guideline is to provide information and advice to women about the diagnosis, treatment and follow-up of uterine sarcomas (with the exception of carcinosarcomas). The guideline focuses on the differentiated management of different subtypes. In addition, the guideline aims to provide a basis for decision-making about the appropriate treatment during interdisciplinary tumor conferences in DKG-certified gynecological cancer centers and sarcoma centers currently being set up.

Targeted areas of patient care

The following sectors are targeted:

• inpatient care

• outpatient care

Target user groups/target audience

The recommendations of the guideline are directed at the following groups of physicians and medical professionals involved in the care of patients with uterine sarcomas:

• gynecologists in private practice

• gynecologists working in hospitals

• pathologists

• radiation therapists

• hemato-oncologists specializing in internal medicine

• pediatric hemato-oncologists

• radiologists

Other target addressees include (for information purposes):

• nursing staff

Adoption and period of validity

The validity of this guideline was confirmed by the executive boards/representatives of the participating professional societies/working groups/organizations/associations as well as by the board of the DGGG, the DGGG Guidelines Commission and the OEGGG and SGGG in December 2020 and was thereby approved in its entirety. This guideline is valid from 1 April 2021 through to 31 March 2024. Because of the contents of this guideline, this period of validity is only an estimate.

III  Methodology

Basic principles

The method used to prepare this guideline was determined by the class to which this guideline was assigned. The AWMF Guidance Manual ( https://www.awmf.org/leitlinien/awmf-regelwerk.html ) has set out the respective rules and requirements for different classes of guidelines. Guidelines are differentiated into lowest (S1), intermediate (S2), and highest (S3) class. The lowest class is defined as consisting of a set of recommendations for action compiled by a non-representative group of experts. In 2004, the S2 class was divided into two subclasses: a systematic evidence-based subclass (S2e) and a structural consensus-based subclass (S2k). The highest S3 class combines both approaches.

This guideline was classified as: S2k

Grading of recommendations

The grading of evidence based on the systematic search, selection, evaluation and synthesis of an evidence base which is then used to grade the recommendations is not envisaged for S2k guidelines. The different individual statements and recommendations are only differentiated by syntax, not by symbols ( Table 3 ).

Tab. 3  Grading of recommendations (based on Lomotan et al., Qual Saf Health Care 2010).

Description of binding character	Expression
Strong recommendation with highly binding character	must/must not
Regular recommendation with moderately binding character	should/should not
Open recommendation with limited binding character	may/may not

Statements

Expositions or explanations of specific facts, circumstances or problems without any direct recommendations for action included in this guideline are referred to as “statements”.

Achieving consensus and level of consensus

At structured NIH-type consensus-based conferences (S2k/S3 level), authorized participants attending the session vote on draft statements and recommendations. The process is as follows. A recommendation is presented, its contents are discussed, proposed changes are put forward, and all proposed changes are voted on. If a consensus (> 75% of votes) is not achieved, there is another round of discussions, followed by a repeat vote. Finally, the extent of consensus is determined, based on the number of participants ( Table 4 ).

Tab. 4  Level of consensus based on extent of agreement.

Symbol	Level of consensus	Extent of agreement in percent
+++	Strong consensus	> 95% of participants agree
++	Consensus	> 75 – 95% of participants agree
+	Majority agreement	> 50 – 75% of participants agree
–	No consensus	< 51% of participants agree

Expert consensus

As the term already indicates, this refers to consensus decisions taken specifically with regard to recommendations/statements issued without a prior systematic search of the literature (S2k) or where evidence is lacking (S2e/S3). The term “expert consensus” (EC) used here is synonymous with terms used in other guidelines such as “good clinical practice” (GCP) or “clinical consensus point” (CCP). The strength of the recommendation is graded as previously described in the chapter on the grading of recommendations; it is only expressed semantically (“must”/“must not” or “should”/“should not” or “may”/“may not”) without the use of symbols.

IV  Guideline

1  Introduction

1.1  Epidemiology, classification, staging

Consensus-based statement 1.S1
Expert consensus	Level of consensus +++
(Homologous) uterine sarcomas are a heterogeneous group of generally rare malignancies (1.5 – 3/100 000) of the uterine muscles, endometrial stroma or uterine connective tissue.

Consensus-based recommendation 1.E1
Expert consensus	Level of consensus +++
References: 1 ,  2
The terminology and morphological diagnosis of uterine sarcomas must be based on the most current edition of the WHO classification.

Consensus-based recommendation 1.E2
Expert consensus	Level of consensus +++
Reference: 2
The postoperative staging of uterine sarcomas must be based on the most current edition of the pTNM classification.

The WHO classification lists the following entities as malignant mesenchymal tumors or malignant mixed epithelial-mesenchymal tumors 2 ,  3 :

• leiomyosarcoma (LMS),

• low-grade endometrial stromal sarcoma (LG-ESS),

• high-grade endometrial stromal sarcoma (HG-ESS),

• undifferentiated uterine sarcoma (UUS),

• adenosarcoma (AS),

• PECome (perivascular epithelioid cell tumor), malignant variant.

The diagnosis of other extremely rare uterine sarcomas (e.g., heterologous sarcomas such as rhabdomyosarcoma) must be based on the WHO classification of soft tissue sarcomas 4 .

This guideline considers the more common entities (LMS, LG-ESS, HG-ESS and UUS or AS, including rhabdomyosarcoma of the uterus in children and adolescents) to the exclusion of the extremely rare forms (rhabdomyosarcoma in adulthood, angiosarcoma, osteosarcoma, chondrosarcoma, liposarcoma, myxofibrosarcoma, alveolar soft tissue sarcoma and epithelioid sarcoma).

The mean patient age at onset of disease is between 50 and 70 years, depending on the tumor type. Identified risk factors include tamoxifen therapy. The incidence of uterine sarcomas is 2 to 3 times higher in women of African descent compared to Asian women or women of European descent.

The staging of uterine sarcomas must be done in accordance with the most current edition of the pTNM classification. Inclusion of the FIGO stage is optional ( Tables 5 and 6 ).

Tab. 5  FIGO and TNM stages for leiomyosarcomas and endometrial stromal sarcomas* of the uterus.

FIGO/TNM stage		Definition
* Tumors simultaneously present in the corpus uteri and the ovary/pelvis accompanied by ovarian/pelvic endometriosis must be classified as independent primary tumors.
I/T1		Tumor limited to the uterus
	IA/T1a	Tumor ≤ 5 cm in greatest dimension
	IB/T1b	Tumor > 5 cm in greatest dimension
II/T2		Tumor extends beyond the uterus, within the pelvis
	IIA/T2a	Involvement of the adnexa (unilateral or bilateral)
	IIB/T2b	Tumor has spread to extrauterine pelvic tissue excluding the adnexa
III/T3		Tumor has infiltrated abdominal tissue
N1	IIIA/T3a	One site
	IIIB/T3b	More than one site
	IIIC	Metastasis of pelvic and/or paraaortic lymph nodes
IV/T4	IVA/T4	Tumor has infiltrated bladder and/or rectum
	IVB	Distant metastasis

Tab. 6  FIGO/TNM stages for adenosarcomas* of the uterus.

FIGO-/TNM stage		Definition
* Tumors simultaneously present in the corpus uteri and the ovary/pelvis accompanied by ovarian/pelvic endometriosis must be classified as independent primary tumors.
I/T1		Tumor limited to the uterus
	IA/T1a	Tumor limited to the endometrium/endocervix without myometrial Infiltration
	IB/T1b	Tumor has infiltrated less than half of the myometrium
	IC/T1c	Tumor has infiltrated ≥ 50% of the myometrium
II/T2		Tumor has spread to the pelvis
	IIA/T2a	Involvement of the adnexa (unilateral or bilateral)
	IIB/T2b	Tumor has spread to extrauterine pelvic tissue excluding the adnexa
III/T3		Intraabdominal tumor spread
N1	IIIA/T3a	One site
	IIIB/T3b	More than one site
	IIIC	Metastasis in pelvic and/or paraaortic lymph nodes
IV/T4	IVA/T4	Tumor has infiltrated bladder and/or rectal mucosa
	IVB	Distant metastasis

1.2  Symptoms, general diagnostic workup (including imaging), general pathology

1.2.1  Symptoms

Consensus-based statement 1.S2
Expert consensus	Level of consensus +++
Uterine sarcomas are not associated with any specific symptoms.

Suspicious symptoms generally include a “rapidly growing uterus” or a fast growing “leiomyoma”, particularly in the post-menopausal period. This criterion has been described several times in the literature 5 ,  6 ,  7 ,  8 . The problem with this, however, is that there is no valid definition of what constitutes “rapid growth” nor has any relevant data been published which would allow clinically relevant evaluation of this parameter in terms of being able to differentiate between myoma and sarcoma.

If there is a clinical suspicion of uterine malignancy, morcellating procedures are contraindicated, even after normal curettage, as they worsen the prognosis 9 . If morcellation is planned, patients must be informed in every case about the risk and must be offered alternative procedures, even cases with tumors which appear to be clinically unsuspicious.

1.2.2  Imaging

Consensus-based recommendation 1.E3
Expert consensus	Level of consensus +++
Because of the high potential for metastasis, histologically confirmed uterine sarcoma should be investigated further, and investigation should include imaging (CT/MRI) of the thorax and abdomen.

Consensus-based statement 1.S3
Expert consensus	Level of consensus ++
Imaging procedures such as sonography and MRI may yield information pointing to the presence of a sarcoma but they are unable to exclude uterine sarcoma.

No imaging procedure (sonography, CT, MRI, PET-CT) has any specific or reliable criteria for detecting sarcomas 10 .

As transvaginal sonography is typically used during normal uterine gynecological examinations, it is the primary diagnostic imaging procedure used to evaluate the uterus.

Indicative changes have also been reported for imaging with MRI which partially correlate with sonographic findings.

Abdominal CT is not suitable to evaluate the primary tumor; it is mainly used for staging or to detect metastasis.

In this context, if the sarcoma has been confirmed, the patient should also always be examined using thoracic CT, which can then serve as the basis for current management of the lesion with the findings used for follow-up.

1.2.3  General pathology

1.2.3.1  Specimens after hysterectomy or surgical therapy of uterine sarcomas

Consensus-based recommendation 1.E4
Expert consensus	Level of consensus +++
References: 2 ,  11 ,  12 ,  13
The morphological workup must include procedures which can gather all of the information listed below. Grading of the histological tumor type based on the WHO classification Grading of ESS (low-grade or high-grade) Evidence for/no evidence of lymph node or blood vessel infiltration (L and V status) Evidence for/no evidence of perineural infiltration (PNI status) Staging (pTNM) Infiltration depth into the myometrium or (endo-)cervical stroma Three-dimensional tumor size, in cm Metric data about the minimal distance between the sarcoma and the respective relevant resection margins R classification (UICC) Estrogen and progesterone receptor expression

Consensus-based recommendation 1.E5
Expert consensus	Level of consensus +++
As uterine sarcomas may be characterized by a high degree of intratumoral heterogeneity, all tumors with a maximum diameter of ≤ 2 cm must be fully investigated. Tumors with diameters > 2 cm must be embedded in paraffin, using one paraffin block per centimeter of the greatest tumor dimension.

Consensus-based recommendation 1.E6
Expert consensus	Level of consensus +++
If the findings do not provide clear information about the malignancy or subtype, a pathological examination must be carried out to investigate the tumor further.

Consensus-based recommendation 1.E7
Expert consensus	Level of consensus +++
All patients diagnosed with uterine sarcoma must be presented to an interdisciplinary tumor conference.

Consensus-based recommendation 1.E8
Expert consensus	Level of consensus ++
The presentation must be carried out at a DKG-certified gynecological cancer center or sarcoma center.

1.3  Genetic predisposition

Consensus-based recommendation 1.E9
Expert consensus	Level of consensus +++
If the patient meets the criteria for germline analysis of the TP53 gene, the patient must be offered genetic counselling with subsequent analysis to exclude a hereditary tumor syndrome.

The overwhelming majority of sarcomas occur sporadically. Nevertheless, a diagnosis of uterine sarcoma in childhood, adolescence or early adulthood can point to a hereditary tumor disposition syndrome, such as Li-Fraumeni syndrome (LFS) or TP53-associated tumor syndrome 14 ,  15 .

2  Uterine Leiomyosarcoma

2.1  Introduction, clinical symptoms and diagnostic workup

In Northern Europe, sarcomas occur in about 0.4 cases/100 000 women across all age groups, with the highest incidence found in women between the ages of 45 and 59 years 16 .

The median age at onset of disease is 50 years 17 .

Clinical symptoms reported by patients may include abnormal bleeding (e.g., mid-cycle bleeding, postmenopausal bleeding) and, depending on the size of the lesion, a sensation of pressure in the vagina or abdomen. The results of curettage and/or endometrial biopsy, e.g., in cases with postmenopausal bleeding, may be false-negative in around 50% of cases and do not allow leiomyosarcoma to be clearly excluded 6 .

2.2  Histopathological diagnosis

Histologically, the WHO classification differentiates between classic (spindle cell) leiomyosarcoma, an epithelioid and a myxoid variant 2 .

Table 7 provides a summary of the diagnostic criteria described in the current WHO classification 2 ,  18 ,  19 .

Tab. 7  Essential diagnostic criteria for uterine leiomyosarcomas 20 ,  21 .

HPF: high power field

Conventional (spindle cell) LMS

→ at least 2 criteria must be met

moderate to high-grade cellular atypia (2+/3+ nuclear atypia) confirmed tumor cell necrosis > 4 mitoses/mm 2 (corresponds to > 10 mitotic figures/10 hpf with a diameter of field of view of 0.55 mm and a field-of-view surface of 0.24 mm 2

Epithelioid LMS

→ at least 1 criterion must be met

moderate to high-grade cellular atypia (2+/3+ nuclear atypia) confirmed tumor cell necrosis > 1.6 mitoses/mm 2 (corresponds to > 4 mitotic figures/10 hpf with a diameter of field of view of 0.55 mm and a field-of-view surface of 0.24 mm 2

Myxoid LMS

→ at least 1 criterion must be met

moderate to high-grade cellular atypia (2+/3+ nuclear atypia) confirmed tumor cell necrosis > 0.4 mitoses/mm 2 (corresponds to > 1 mitotic figure/10 hpf with a diameter of field of view of 0.55 mm and a field-of-view surface of 0.24 mm 2 infiltrative tumor borders or irregular lesion border

2.3  Prognosis

LMS is a highly aggressive tumor with an unfavorable prognosis. The recurrence rates range from 53 to 71% and the mean 5-year survival rate is between 40 and 50% 22 ,  23 .

Additional prognostic factors include patient age, tumor resection margins, mitotic index and vascular invasion 22 ,  24 . The most important iatrogenic negative prognostic factor is tumor injury, for example, caused by morcellation, perforation and/or “myomectomy” 25 .

2.4  Surgical treatment

Consensus-based recommendation 2.E10
Expert consensus	Level of consensus ++
If the sarcoma is limited to the uterus, the uterus must be completely resected without morcellation or injury to the uterus. The ovaries should be retained if the patient is premenopausal. The ovaries may be retained in postmenopausal patients.

Consensus-based recommendation 2.E11
Expert consensus	Level of consensus +++
Systematic pelvic and paraaortic lymphadenectomy should not be carried out if the lymph nodes are diagnostically unremarkable.

Complete hysterectomy is the gold standard for the surgical management of leiomyosarcoma limited to the uterus. There are no data which suggest that resection of the adnexa could result in a better prognosis. Therefore, resection of the adnexa should especially not be carried out in premenopausal patients. The adnexa may also be retained in postmenopausal patients; under no circumstances should a second surgical intervention be carried out if the adnexa were retained during the primary intervention 24 ,  26 ,  27 . Ovarian metastasis is rare, with an incidence of just 3%, and occurs almost exclusively in cases with intraperitoneal spread 27 .

Irrespectively of the above, the option of an opportunistic salpingectomy should be discussed with the patient in the context of discussing the primary intervention.

The incidence of primary pelvic and paraaortic lymph node metastasis is low in cases with leiomyosarcoma. If lymph node involvement is present (often already detected intraoperatively), then extrauterine or hematogenic metastasis is usually already present. This means that systematic pelvic and paraaortic lymphadenectomy will not be associated with a better prognosis and it is generally not recommended 26 ,  28 ,  29 .

2.5  Adjuvant systemic therapy and radiotherapy

Consensus-based recommendation 2.E12
Expert consensus	Level of consensus ++
Adjuvant chemotherapy should generally not be administered to treat leiomyosarcoma. Depending on the presence of other risk factors (e.g., higher tumor stage), adjuvant chemotherapy may be administered in individual cases.

Consensus-based recommendation 2.E13
Expert consensus	Level of consensus +++
Radiotherapy should not be carried out after complete resection of a stage I/II leiomyosarcoma.

Adjuvant systemic therapy is not generally indicated as, up to now, no randomized controlled study has been able to provide evidence for any benefit in terms of overall survival. This was also confirmed by a meta-analysis 30 ,  31 .

A prospective randomized phase III study, which was unfortunately halted after the inclusion of just 81 patients (53 × LMS, 9 × HG-ESS, and 19 stage I – III carcinosarcomas) due to a lack of recruitment, reported a significantly higher 3-year progression-free survival (PFS) rate (55 vs. 41%) following the administration of polychemotherapy consisting of doxorubicin/ifosfamide/cisplatin in addition to radiotherapy, but this had no effect on overall survival rates 32 . The heterogeneous patient cohort and the lack of an observation arm has made it impossible to come to definitive conclusions 32 .

Another prospective study 33 , which analyzed outcomes after the administration of a combination of gemcitabine and docetaxel, provided some evidence for potential effectiveness in an adjuvant setting. But because the study included all stages (I – IV), this has significantly limited conclusions about tumors which are limited to the uterus.

A consecutive prospective one-arm phase II study by the same working group which investigated tumors limited to only the uterus treated with gemcitabine plus docetaxel followed by doxorubicin showed a longer PFS (57% 3-year PFS) compared to historic controls 34 .

A phase III study which aimed to build on these data also had to be discontinued after the inclusion of just 38 patients because of the difficulty in recruiting more participants 35 .

Based on these results, adjuvant chemotherapy to treat higher-stage disease may at least be discussed in individual cases, even if it has not been possible to date to show evidence for a significant improvement in the overall survival rate.

A randomized study 36 reported that adjuvant radiotherapy of the pelvis with 50.4 Gy in cases with stage I or II disease resulted in better local control in the overall patient collective with different sarcoma entities, but no effect on the rate of local recurrence (20% with radiotherapy or 24% without radiotherapy) or on the overall survival was detected in the subgroup of patients with leiomyosarcoma (n = 99). This means that radiotherapy is not generally indicated following complete resection of a stage I/II leiomyosarcoma. Radiotherapy can be considered in cases with R1/2 resection and locally advanced disease if the tumor is limited to the pelvis. However, there are no valid studies showing a significant verifiable effect on overall survival.

2.6  Therapy for metastasis and recurrence

Consensus-based recommendation 2.E4
Expert consensus	Level of consensus +++
In cases with recurrence and/or metastasis of a LMS, maximum surgical cytoreduction should be considered to achieve tumor clearance.

Consensus-based recommendation 2.E5
Expert consensus	Level of consensus +++
If the diagnosis is metastasized leiomyosarcoma, the first-line therapy must consist of doxorubicin.

There are some indications that complete surgical resection in cases of recurrence of metastasis of uterine leiomyosarcoma is associated with a better prognosis compared to chemotherapy alone and/or radiotherapy 37  –  40 . Two studies carried out in a selected patient cohort reported better survival (median survival 45 vs. 31 months or 2.0 vs. 1.1 years) after complete resection of metastases in patients with leiomyosarcoma 37 ,  41 . The resection, particularly of individual lung and/or liver metastases, could prolong survival in selected patients 42 ,  43 ,  44 .

Palliative systemic therapy is indicated for patients with diffuse metastasis and recurrence/metastasis which cannot be (can no longer be) treated with surgery. Such a therapy should be discussed in detail with the patient and the associated toxicity should be carefully considered.

There are only a few substances such as ifosfamide, gemcitabine or doxorubicin that are effective for mono-chemotherapy, and they have moderate response rates (partial or complete remission) of between 17% and 25% 45 ,  46 .

Paclitaxel, cisplatin, topotecan and etoposide are not very effective and have low response rates of less than 10% 47 ,  48 ,  49 ,  50 .

In contrast, combination chemotherapies have higher response rates compared to monotherapies but they are also associated with a higher toxicity 51 ,  52 ,  53 .

Only one prospective randomized phase II trial has shown that combination therapy is superior to mono-chemotherapy in terms of survival; therapy consisted of a combination of docetaxel/gemcitabine and was compared to monotherapy with gemcitabine 54 . However, another study with a comparable study design was unable to replicate the results, so that ultimately it is still not clear whether this combination offers a benefit for patients 55 .

According to more recent data from a phase III study, a combination of docetaxel and gemcitabine offered no benefit compared to monotherapy with doxorubicin to either the overall patient population with soft-tissue sarcomas or to the subgroup with uterine LMS (median overall survival 67 vs. 76 weeks, HR 1.14, 95% CI 0.83 – 1.57; p = 0.41 for the overall patient population, n = 257) 56 .

The use of trabectedin for second-line chemotherapy in a metastatic setting following the administration of anthracyclines has been studied in phase II trials and should be the drug of choice for this indication. Although the rate of remission is low, stabilization of disease was achieved in up to 50% of cases 57 .

Pazopanib, a multiple tyrosine kinase inhibitor, is a further second-line therapy option which has been investigated in a double-blind placebo-controlled phase III study, although patients with sarcoma types with varying histologies were included in the study. As regards the rate of remission and the percentage of patients who experienced stabilization of disease, the same statement applies to pazopanib as for trabectedin. In the study, pazopanib significantly increased the progression-free survival interval in both the overall patient population and in the subgroup of patients with LMS 58 .

3  Low-grade Endometrial Stromal Sarcomas

3.1  Introduction, clinical symptoms, diagnostic workup

The median age at onset of disease is the 6th decade of life 17 .

These tumors typically manifest as mid-cycle or postmenopausal bleeding, sometimes accompanied by an enlarged uterus and the corresponding symptoms.

The WHO classification differentiates malignant endometrial stromal tumors into

• low-grade endometrial stromal sarcomas,

• high-grade endometrial stromal sarcomas, and

• undifferentiated uterine sarcomas 59 .

3.2  Prognosis

The general prognosis for LG-ESS is favorable but depends on the initial tumor stage at diagnosis 60 . The disease-specific 5-year survival rate for low-grade ESS ís 80 – 90% and the 10-year survival rate is around 70% 61 ,  62 . If the tumor is limited to the uterus at the time of diagnosis (stage I), the rates are 100% and 90%, respectively. The survival rate decreases to around 40% for higher stage disease 29 .

Positive hormone receptors are a favorable prognostic factor with regard to overall survival 63 .

3.3  Surgical treatment

Consensus-based recommendation 3.E6
Expert consensus	Level of consensus ++
In cases which are suspicious for sarcoma limited to the uterus, treatment must consist of complete resection of the uterus without morcellation or injury to the uterus.

Consensus-based recommendation 3.E7
Expert consensus	Level of consensus +++
Reference: 64
There are no data available about the oncological safety of using hormone replacement therapy after primary treatment of a low-grade ESS. Because of the tumor biology of low-grade ESS and its high estrogen dependency, hormone replacement therapy should not be recommended.

Consensus-based recommendation 3.E8
Expert consensus	Level of consensus +++
Systematic pelvic and paraaortic lymphadenectomy should not be carried out in cases with diagnostically unremarkable lymph nodes.

The therapy of choice is complete hysterectomy without injury to the uterus or morcellation 65 .

There is a lot of evidence about the endocrine dependence of LG-ESS and the pronounced expression of hormone receptors. The question arises in this context, particularly in premenopausal patients, whether bilateral removal of the adnexa should also be carried out. A retrospective analysis of 153 LG-ESS patients reported a significantly higher rate of recurrence when the ovaries were retained in premenopausal patients. But the analysis did not differentiate between cases with complete resection of the tumor and cases with incomplete resection. Moreover, neither this analysis nor two further evaluations of the SEER database found that leaving both adnexa in situ had a negative effect on overall survival. A meta-analysis of 17 studies with a total of 786 patients came to the same conclusion 66 . The benefits of ovarian preservation in younger patients should therefore be carefully weighed against the risk of a higher probability of recurrence and critically discussed with affected patients 67 ,  68 ,  69 .

Lymph node involvement is rare and does not appear to have an effect on prognosis. Systematic lymphadenectomy and any adjuvant therapy options based on systematic lymphadenectomy are therefore not expected to extend survival, meaning that lymphadenectomy cannot be routinely recommended 10 ,  62 ,  69 ,  70 .

3.4  Adjuvant systemic therapy and radiotherapy

Consensus-based recommendation 3.E9
Expert consensus	Level of consensus +++
Adjuvant endocrine therapy should not generally be carried out for low-grade ESS but may be administered in individual cases, depending on the presence of other risk factors (e.g., higher tumor stage).

Consensus-based recommendation 3.E10
Expert consensus	Level of consensus +++
Adjuvant chemotherapy must not be administered.

Consensus-based recommendation 3.E11
Expert consensus	Level of consensus +++
Adjuvant radiotherapy must not be carried out.

Postoperative adjuvant endocrine therapy may be discussed with patients with higher tumor stages or after accidental morcellation, although prospective studies are lacking. A meta-analysis came to the conclusion that postoperative adjuvant endocrine therapy results in a significantly lower risk of recurrence but it has no effect on the overall survival. But the validity of these results is limited by the heterogeneity of the patient population without or with postoperative residual tumor 71 . The data from comparative retrospective analyses of adjuvant therapy support the use of either medroxyprogesterone acetate 200 mg/day (in Germany only available as 250 mg doses) or megestrol acetate 80 – 160 mg/day or, alternatively, an aromatase inhibitor (letrozole 2.5 mg/day, anastrozole 1 mg/day or exemestane 25 mg/day). The prerequisite for this is confirmed adequate expression of hormone receptors. The duration of adjuvant therapy has not been sufficiently studied. A duration of 5 years is currently being discussed 72 ,  73 ,  74 .

There are no valid data available for adjuvant chemotherapy.

A first SEER analysis of 3650 patients with uterine sarcomas found that percutaneous pelvic radiotherapy (± brachytherapy) had a significant positive effect on the rate of local recurrence for both the total patient population 75 and for the subgroups of patients with ESS (n = 361: 97% vs. 93% after 5 years or 97% vs. 87% after 8 years) but had no impact on overall survival. A specific SEER analysis of 1010 patients with ESS was also unable to confirm that adjuvant radiotherapy had a significant benefit on overall survival 62 . The only randomized study on pelvic radiation for uterine sarcoma 36 which included 30 patients with endometrial stromal sarcoma did not carry out a separate survival analysis for this subgroup. Because of the unclear data and the medium and long-term side effects of adjuvant radiotherapy when loco-regional control is already good, adjuvant radiotherapy is not indicated.

3.5  Therapy for metastasis and recurrence

Consensus-based recommendation 3.E12
Expert consensus	Level of consensus +++
Maximum surgical cytoreduction may be considered in cases with recurrence and/or metastasis to achieve tumor clearance.

Consensus-based recommendation 3.E23
Expert consensus	Level of consensus +++
Tamoxifen is contraindicated for LG-ESS.

LG-ESS usually has a significantly better prognosis than LMS. However, recurrence is possible even after several decades 76 . In every case of recurrence or metastasis it is important to check whether surgery with the aim of complete macroscopic resection is possible 77 . Because of their slow growth, repeated resections of a low-grade endometrial stromal sarcoma may offer a benefit 10 .

After surgical resection, the option of anti-endocrine therapy should be discussed with the patient. The prerequisite for this therapy is confirmed adequate expression of hormone receptors.

Anti-endocrine therapy should be recommended to all patients with postoperative residual tumor, inoperable recurrence or multiple distant metastasis. Because of the high expression of estrogen and progesterone receptors, progestogens or aromatase inhibitors are used for treatment 78 ,  79 ,  80 ,  81 .

Retrospective analyses of small cases series indicated that medroxyprogesterone acetate 200 mg/day (available in Germany as 250 mg doses) or megestrol acetate 160 mg/day are effective. Response rates of up to 82% have been reported 79 . Alternatively, although less data are available, aromatase inhibitors (letrozole 2.5 mg/day, anastrozole 1 mg/day or exemestane 25 mg/day) also appear to exert a positive effect (60% remission and 40% stable disease after a median follow-up of 4 years) (in Germany this is an off-label use) 73 ,  80 .

Because it is a risk factor for uterine sarcoma, tamoxifen must not be used for endocrine therapy 82 . Any ongoing tamoxifen therapy must be discontinued, and if tamoxifen is indicated for breast cancer, it must be replaced by an aromatase inhibitor.

Targeted percutaneous radiotherapy may be used as palliative therapy for recurrence/metastasis which cannot be completely resected 83 ,  84 .

4  High-grade Endometrial Stromal Sarcomas and Undifferentiated Uterine Sarcomas

4.1  Introduction, clinical symptoms and diagnostic workup

Although there are clear pathological anatomical differences between HG-ESS and UUS, both entities share a number of similarities with regard to incidence, clinical presentation, prognosis and even therapy, which is why they are discussed together here. The staging corresponds to that used for LMS.

The median age at onset of disease is 60 years. The tumors typically manifest as pathological bleeding, sometimes accompanied by an enlarged uterus and related symptoms. Because of the aggressiveness of the tumor, the diagnosis is often only made at an advanced stage of disease.

4.2  Prognosis

As regards prognosis, the prognosis for HG-ESS is much closer to that of highly aggressive undifferentiated uterine sarcomas (UUS) rather than the more favorable prognosis of LG-ESS 85 . Studies have shown that a threshold value of > 25 mitotic figures in 10 hpf is prognostically relevant 86 ,  87 .

Because disease is often only detected at an advanced stage, the prognosis is generally unfavorable with a median overall survival of 1 – 3 years 88 ,  89 ,  90 .

4.3  Surgical treatment

Consensus-based recommendation 4.E24
Expert consensus	Level of consensus +++
If the sarcoma is limited to the uterus, the uterus must be completely resected without morcellation or injury to the uterus. The ovaries should be retained if the patient is premenopausal. The ovaries may be retained in postmenopausal patients.

Consensus-based recommendation 4.E25
Expert consensus	Level of consensus +++
Systematic pelvic and paraaortic lymphadenectomy should not be carried out if the lymph nodes are diagnostically unremarkable.

Complete hysterectomy (without morcellation or injury of the uterus) is the therapy of choice. The benefit of bilateral adnexa resection has not been confirmed and is questionable, given the lack of hormone receptor expression in most HG-ESS. The adnexa may therefore be retained in premenopausal patients.

Although positive pelvic and/or paraaortic lymph nodes are associated with a poorer prognosis, according to an analysis of the SEER database, lymphadenectomy is not associated with a better survival 62 .

4.4  Adjuvant systemic therapy and radiotherapy

Consensus-based recommendation 4.E26
Expert consensus	Level of consensus +++
Adjuvant chemotherapy should not be generally administered to patients with HG-ESS/UUS, but may be administered in individual cases depending on the presence of additional risk factors (e.g., high tumor stage). Radiotherapy should not be carried out after complete resection of HG-ESS/UUS.

There are no valid prospective data for adjuvant chemotherapy. However, multivariate analysis carried out in a retrospective analysis of 39 patients in the French Sarcoma Group showed that chemotherapy was associated with a significant survival benefit 90 . This means that adjuvant chemotherapy may be discussed in individual cases, particularly cases with advanced stage disease, but patients must be informed about the related side effects and the lack of evidence confirming its efficacy.

The data on the benefit of adjuvant radiotherapy is limited and heterogeneous.

A multicenter retrospective analysis investigated 59 patients with endometrial stromal tumors, 29 of whom had undifferentiated uterine sarcomas (58% with stage I or II disease 91 ). 86% of patients were given pelvic teletherapy (median dose for the overall patient population was 48 Gy) and 51% had brachytherapy. The overall survival rate of patients with undifferentiated uterine sarcomas was 65% at 5 years and locoregional control was achieved in 40% of patients. Multivariate analysis found that pelvic radiotherapy was associated with a significantly better overall survival of the total patient population (endometrial stromal sarcoma and undifferentiated uterine sarcoma).

A retrospective analysis of 39 patients in the French Sarcoma Group came to similar conclusions 90 .

In contrast, a detailed analysis of the SEER database found that postoperative radiotherapy offered no survival benefit to patients (HG-ESS and LG-ESS, all stages of disease) 62 .

However, because of the heterogeneous patient cohorts, low case numbers and retrospective nature of the studies, it is not possible to draw definitive conclusions.

4.5  Therapy for metastasis and recurrence

Chemotherapy for this tumor entity is analogous to that for LMS, although specific data are limited.

There are some indications that certain recurrences are histologically heterogeneous (displaying aspects of high and low-grade tumors) and that in tumors with evidence of receptors, endocrine therapy only affects the low-grade part, while the high-grade part which determines prognosis is not affected by hormone therapy 92 .

In contrast to LG-ESS, endocrine therapy does not play any role.

5  Uterine Adenosarcomas

5.1  Introduction, clinical symptoms and diagnostic workup

This rare entity occurs in all age groups 93 but peaks in the 6th and 7th decade of life. As adenosarcomas (AS) develop in the endometrium, they often take the form of polyps in the uterine cavity 94 . In the majority of cases, the symptoms of AS are therefore similar to those of endometrial carcinomas and consist of mid-cycle or postmenopausal bleeding, possibly accompanied by an enlarged uterus and related symptoms. In contrast to most other uterine sarcomas, AS present on imaging as (polypoid) intracavitary tumors.

Because of its exposed location in the uterine cavity as described above, in the majority of cases AS are correctly identified as malignancies during hysteroscopy/curettage 95 .

According to the WHO classification, adenosarcomas (AS) are defined as epithelial-mesenchymal tumors with benign epithelial and malignant mesenchymal components 20 ,  79 ,  80 ,  96 ,  97 . In ~ 90% of cases, the mesenchymal component has a low-grade histology. If the mesenchymal component can be confirmed in more than 25% of the total tumor area or if there is a high-grade sarcomatous component, the diagnosis is AS with sarcomatous overgrowth (SO) 98 ,  99 .

5.2  Prognosis

The recurrence rate for adenosarcoma without sarcomatous overgrowth is 15 – 25%, but the recurrence rate for cases with sarcomatous overgrowth is 45 – 70%. A higher rate of recurrence has also been observed for deep myometrial invasion, lymph node invasion, highly malignant heterologous stromal component and/or extrauterine spread. The mortality rate for a typical adenosarcoma is 10 – 25%, but it can be as high as 75% in cases with sarcomatous overgrowth.

5.3  Surgical treatment

Consensus-based recommendation 4.E27
Expert consensus	Level of consensus +++
If the sarcoma is limited to the uterus, the uterus must be completely resected without morcellation or injury to the uterus.

As with the other sarcomas, the treatment of choice consists of complete hysterectomy without injury to the uterus or morcellation.

It is not clear whether the adnexa should also be removed. An analysis of the SEER database (n = 162 patients with adenosarcomas) found that bilateral adnexa resection had no impact on survival 27 .

The value of systematic pelvic and paraaortic lymphadenectomy is also not clear 72 . The probability of lymph node involvement is only 3 – 4% 100 .

Because of this low incidence and the fact that lymph node status had no effect on patient survival in this analysis, systematic lymphadenectomy is not routinely recommended.

5.4  Adjuvant systemic therapy and radiotherapy

To date, no benefit has been reported for any adjuvant therapy. Based on 1884 cases in the National Cancer Database, chemotherapy has no effect on survival and postoperative radiotherapy even had a negative effect on survival 100 .

As with other uterine sarcomas, neither adjuvant chemotherapy nor radiotherapy are currently indicated after complete surgical resection.

If surgical resection was incomplete or in cases with advanced disease, treatment in cases with sarcomatous overgrowth should be based on treatment for HG-ESS while treatment in cases without sarcomatous overgrowth and with confirmed expression of hormone receptors should be similar to that for LG-ESS. As with LG-ESS, tamoxifen is contraindicated.

5.5  Therapy for metastasis and recurrence

It has been reported that complete surgical resection is associated with better survival rates (26 vs. 15 months) in cases of recurrence or metastasis of AS 101 .

Because of the above, as with other uterine sarcomas, it is recommended to check whether surgery aiming for complete macroscopic resection is possible.

There is no optimal regimen for systemic therapy. Recurrence of adenosarcoma with sarcomatous overgrowth should be treated with chemotherapy in the same way as HG-ESS 102 . Recurrence of adenosarcoma without sarcomatous overgrowth but with hormone receptor expression should be treated with endocrine therapy in the same way as LG-ESS.

6  Rhabdomyosarcomas of the Uterus in Children and Adolescents

In childhood and adolescence, the predilection sites for rhabdomyosarcoma are the vagina, cervix and uterus. Around 10% of all rhabdomyosarcomas detected in girls occur in the female genital tract. The median age at diagnosis is 1.9 years for vaginal, 2.7 years for uterine and 13.5 years for cervical rhabdomyosarcomas. 97% of all rhabdomyosarcomas of the female genital tract present with non-alveolar histological findings. 5% of all patients have regional lymph node involvement. Survival rates of children are very good (event-free 10-year survival: 74%; 10-year overall survival: 92%) 103 ,  104 .

The presence of a mass in the vagina, cervix and/or uterus in a child or adolescent is always suspicious for rhabdomyosarcoma. A biopsy must be carried out to confirm the diagnosis in all cases, and mutilating surgery should be avoided 103 . The required multimodal treatment should be carried out in a center for pediatric oncology in accordance with the guidelines of the Joint Federal Committee of Germany (Section 136 para. 1 sentence 1 no. 2, vol. V of the German Social Insurance Code [SGB V]).

The following diagnostic measures are recommended for staging: thoracic CT, ultrasound or MRI of the abdomen and pelvis to obtain images of the efferent lymph nodes, bone marrow biopsies carried out at two different sites and a bone scan 105 .

The initial risk stratification is based on the following clinical parameters ( Table 8 ).

Tab. 8  Risk stratification based on clinical parameters for rhabdomyosarcomas.

Risk	Parameter
Low risk	Non-alveolar histology
Tumor diameter ≤ 5 cm and age at diagnosis < 10 years
N0, M0
primary R0 resection
Standard risk	Non-alveolar histology
N0, M0
primary R1/R2 resection
High risk	Non-alveolar histology and N1
Alveolar histology and N0
M0
Very high risk	Alveolar histology and N1
M0
Systematic metastasis	M1

After biopsy has confirmed the diagnosis, primary surgery should only be attempted if organ-preserving R0 resection is possible. All other tumors must be treated with neoadjuvant polychemotherapy. The intensity of chemotherapy depends on the initial risk stratification 103 ,  105 .

The definitive local therapy should be carried out after 10 weeks of neoadjuvant chemotherapy. Mutilating surgery should be avoided 103 ,  105 .

If the initial surgery results in R0 resection, adjuvant radiotherapy is not indicated in cases with non-alveolar tumors 103 ,  105 . Otherwise, adjuvant radiotherapy in the form of organ-preserving surgery combined with brachytherapy carried out in specialized centers should be considered 103 ,  106 .

All children and adolescents with rhabdomyosarcoma of the female genital tract should receive adjuvant chemotherapy 103 ,  105 . The indication for adjuvant chemotherapy does not depend on when resection was carried out or on the resection status. The intensity of chemotherapy depends on the initial risk stratification and the resection result 103 ,  105 .

Maintenance chemotherapy is additionally recommended in cases with metastatic disease, lymph node involvement and/or alveolar histology 6 .

7  Follow-up

Consensus-based recommendation 7.E28
Expert consensus	Level of consensus +++
In the first 2 – 3 years after primary therapy, patients should have a regular follow-up examination every three months with follow-up consisting of speculum examination, vaginal and rectal examination and, if necessary, ultrasound.

Consensus-based recommendation 7.E29
Expert consensus	Level of consensus +++
An additional diagnostic workup consisting of imaging for the early detection of metastasis can be beneficial.

Follow-up serves to secure the success of treatment and preserve the patientʼs quality of life.

It is not clear whether local intervention following the early detection of unilocular recurrence/metastasis results in an improvement of overall survival.

Nevertheless, as part of the additional diagnostic workup for the early detection of metastasis, imaging can be used as it may improve the chances of achieving complete resection (cf. the specific chapters on individual entities).

8  Morcellation

Consensus-based recommendation 8.E30
Expert consensus	Level of consensus +++
The use of morcellation techniques to treat uterine sarcomas results in a worse prognosis. Patients must be informed of this.

Consensus-based recommendation 8.E31
Expert consensus	Level of consensus +++
Morcellation must not be carried out in a postmenopausal patient if the patient has been diagnosed with a newly developed “myoma”, a large rapidly growing “myoma” or a “myoma” which has become symptomatic for the first time.

Consensus-based recommendation 8.E32
Expert consensus	Level of consensus +++
Contained in-bag morcellation cannot exclude the dissemination of tumor cells.

Consensus-based recommendation 8.E33
Expert consensus	Level of consensus +++
Patients who had a morcellation procedure to remove a uterine sarcoma must present to a DKG-certified gynecological cancer center very soon after the morcellation procedure.

Consensus-based recommendation 8.E34
Expert consensus	Level of consensus +++
Systemic therapy should not generally be carried out after morcellation; nevertheless, systemic therapy may be administered because of the higher risk of recurrence after morcellation.

Irrespective of the surgical approach, morcellation of what is presumed to be benign tissue can occur during uterus-preserving surgery to manage fibroid myomas or during total or subtotal hysterectomy procedures, and postoperative examination of the resected specimen may reclassify it as a uterine sarcoma.

The prevalence of previously unknown uterine sarcomas detected during hysterectomy or myoma procedures varies in the literature; it is reported to be between 1/204 and 1/7400 (0.49 – 0.014%). A summary analysis of the rate of accidentally operated uterine sarcomas reported in 10 international studies with 8753 surgical procedures resulted in an incidence of 0.24% 107 . A meta-analysis of 10 120 patients from 9 studies reported a comparable incidence for accidentally operated uterine sarcomas of 0.29% 108 . A German analysis published in 2017 of 475 morcellation procedures carried out from 2004 to 2014 found a risk of 0.35% (1/280) for the accidental morcellation of a previously unknown uterine sarcoma during hysterectomy and no case of uterine sarcoma during 195 myoma morcellation procedures (0/195) 109 . Another German study of 10 731 LASH procedures reported a rate of 0.06% for uterine sarcomas and 0.07% for endometrial carcinomas 110 . One of the largest series with a total of 26 643 patients included 88 cases with uterine sarcoma (prevalence 0.33%), of which 29 were LMS, 48 were ESS and 11 were adenosarcomas 111 .

Endoscopic intraabdominal morcellation of undetected sarcomas during hysterectomy procedures, conservative surgical management of uterine myomas and laparoscopic supracervical hysterectomy (LASH) procedures are particularly associated with a worse oncological prognosis in terms of recurrence-free survival and overall survival 5 ,  7 ,  107 ,  112 ,  113 ,  114 ,  115 .

A systematic review of the literature and meta-analysis of 4 studies with 202 patients (75 with and 127 without morcellation) published in 2015 reported a higher rate of recurrence after morcellation (62% versus 39%; odds ratio [OR] 3.16; 95% confidence interval [CI] 1.38 – 7.26) and a higher rate of intraabdominal recurrence (39% versus 9%; OR 4.11; 95% CI 1.92 – 8.81). The overall survival rate after morcellation was also significantly lower (48% versus 29%; OR 2.42; 95% CI 1.19 – 4.92) 116 . However, there was no difference in the rate of extra-abdominal recurrence. These data have been confirmed by further studies 9 ,  117 ,  118 ,  119 ,  120 but not by all 121  –  124 . In a large retrospective series of 843 occult endometrial carcinomas and 334 occult uterine sarcomas, the cancer-specific 5-year mortality after hysterectomy with morcellation was significantly higher compared to procedures without morcellation (hazard ratio [HR] 2.66; 95% CI 1.11 – 6.37) 111 . But this association was limited to uterine sarcomas and was not found for endometrial carcinomas.

Because of this increased risk of recurrence after morcellation, systemic therapy may be administered even though there is no evidence that it can improve the prognosis again.

Accidental morcellation during vaginal hysterectomy does not appear to increase the risk of recurrence. Wasson et al. analyzed 2296 vaginal hysterectomies, with morcellation carried out in 611 cases 125 . The incidence of accidentally morcellated malignancies was 0.82% (5/611); 3 cases were endometrial carcinoma and 2 cases were sarcoma. No recurrence was observed in any of the 5 cases. Another analysis of more than 3000 hysterectomies with a total of 18 sarcomas confirmed the observation that transvaginal morcellation does not increase the rate of recurrence 126 . It should be noted, however, that all of these studies were retrospective observational studies.

It is not possible to definitively exclude uterine sarcoma preoperatively based on clinical symptoms, growth patterns, ultrasound, CT, PET-CT or MRI 107 ,  127 . The risk score proposed by the International Society for Gynecologic Endoscopy (ISGE) is only based on a summary of clinical and ultrasound or MRI criteria taken from the literature 7 . The score has not yet been validated in a prospective patient population. The same applies to the rPRESS score developed by Zhang and colleagues 128 , which is additionally based on very small number of cases 129 . Significantly higher case numbers (826 patients with leiomyomas or 293 patients with LMS) were analyzed for the score developed by Köhler and colleagues 8 . However, their study only collected retrospective data for LMS, and no prospective validation of the score has yet been done.

The use of these scores is therefore not recommended.

Caution is always warranted if risk factors are present: in addition to age, a generally acknowledged risk factor for uterine sarcoma is ongoing or completed tamoxifen therapy 130 .

Hereditary tumor syndromes such as Li-Fraumeni syndrome (which is associated with sarcoma), or Lynch syndrome and PTEN syndrome (which are associated with endometrial carcinoma) are also contraindications for morcellation 131 .

The occurrence of sonographically visible or palpable uterine tumors in the postmenopausal period is unphysiological as is increased growth of a known “myoma”. Although none of these factors have been confirmed, either in isolation or in combination, as risk factors for uterine sarcoma, from a clinical and pathophysiological perspective, it may be wise to assume that such cases have an increased risk of uterine sarcoma.

The use of contained in-bag morcellation to prevent the dissemination of malignant cells during morcellation surgery has been described in various studies 132 ,  133 ,  134 ,  135 . But contained in-bag morcellation has still not been clinically validated, meaning that it is not possible to make a reliable statement about the oncological safety of this technique 7 ,  107 ,  115 . A recent analysis of the Cochrane database published in 2020 found no evidence that contained in-bag morcellation for intracorporeal or extracorporeal morcellation is an effective or safe procedure 136 .

As regards the appropriate procedure after morcellation of a sarcoma, the choice of approach should be guided by the statements in the position paper issued by the German Society for Gynecology and Obstetrics 107 and by international recommendations and statements 5 ,  7 ,  112 ,  113 ,  114 ,  115 . These statements also apply to open or endoscopic tumor resections, irrespective of whether morcellation is carried out or not 122 . The consensus is that the appropriate oncological surgery recommended for the individual tumor entity should be carried out as soon as possible. It has not been confirmed whether this approach affects overall survival.

9  Information for patients

Consensus-based recommendation 9.E35
Expert consensus	Level of consensus +++
The patient must be offered the option to include her partner or family members in talks and discussions.

Consensus-based recommendation 9.E36
Expert consensus	Level of consensus +++
The patient must be informed about the option of contacting self-help groups.