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Abstract

Uterine sarcomas include a variety of mono- and biphasic malignancies, whereas tumor biology varies from an indolent and hormone-sensitive growth pattern to an aggressive and nonresponsive disease that is inevitably fatal. Insight into these different entities has only been gained after careful analysis of clinical, pathologic and molecular characteristics during the last few years. Furthermore, the rarity of uterine sarcomas has motivated many to collect data from different subtypes and to report on the collective data in order to report on larger numbers. The current overview aims to provide insights of clinical importance into each type of uterine sarcoma, with a special emphasis on treatment modalities.

Keywords

carcinosarcoma chemotherapy endometrial stromal sarcoma hormonal leiomyosarcoma surgery treatment undifferentiated sarcoma

Other than fibroids, mesenchymal tumors are uncommon, since sarcomas of the uterus comprise only 3% of uterine malignancies [1]. Uterine sarcomas encompass leiomyosarcomas (LMSs), carcinosarcomas (CSs), adenosarcomas, endometrial stromal sarcomas (ESSs) and undifferentiated uterine sarcomas (UUSs). Although evidence from the last two decades suggests an epithelial origin of carcinosarcoma [2], the authors will also discuss this entity. Preceeded by a short introduction on origin and pathology, the role of different treatment options will be discussed for each tumor type. Globally, it should be remembered that most studies in uterine sarcoma include relatively few data and that, too frequently, a mix of tumors is included. Nevertheless, sufficient clinical and therapeutic evidence is available on a divergent and interesting group of malignancies.

Endometrial stromal sarcoma

Endometrial stromal neoplasms are composed of cells that resemble proliferative phase or hyper-plastic endometrial stromal cells [3,4]. Benign endometrial stromal tumors are known as stromal nodules, while their malignant counterparts are termed ESSs. A distinction is made on the basis of circumscribed and expansile growth in the former, but invasion of myometrium and vascular spaces in the latter [1]. ESSs have traditionally been stratified on the basis of the mitotic index into low- and high-grade tumors. However, high-grade tumors lack the typical growth pattern and vascularity of low-grade ESS and show destructive myometrial invasion rather than the permeate invasion of low-grade ESS. Moreover, they demonstrate marked cellular pleomorphism and brisk mitotic activity. As a result, the division of ESS into low- and high-grade has fallen out of favor and the designation ESS is now considered best restricted to malignancies that were formally referred to as low-grade stromal sarcomas [5]. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype are almost invariably high grade [5], and are termed poorly differentiated or UUSs. Therefore, the classification of uterine sarcoma as high-grade ESS should be abandoned [6].

It is estimated that 86% of ESSs present as stage I–II disease (limited to the uterus) [7]. Pelvic or abdominal recurrences in stage I disease develop in a third to a half of patients [7,8]. The tumors typically have an indolent growth with a tendency for late recurrence. In one large series, the interval before recurrence varied from 3 months to 23 years, with a median interval of 3 years [8]. In the largest clinicopathologic study to date on ESS, the median time between hysterectomy and relapse was 5.4 years and 9 month for stages I and III–IV, respectively [7].

Since cytotoxic treatments are more active against rapidly dividing cells, low-grade malignancies are preferentially treated by surgery. Whether the removal of the uterus for ESS should be associated with bilateral salpingo-oophorectomy is uncertain, since conflicting results have been reported [9,10]. However, given the high recurrence rates, even in early stage disease, it is suggested that both ovaries be removed in peri- or postmenopausal women. In very young women, the risk of recurrence should be balanced against the risk of estrogen deprivation and a decision should be taken on an individual basis.

Little data are available on adjuvant treatment modalities in ESS. In a recent report, women receiving surgery followed by progestins were less likely to experience recurrent disease [10]. These results are important, since no previous results are available, but given the low number of women taking part in the study they should be confirmed in larger trials. Furthermore, the promising results in a small number of patients should be balanced against the side effects (mainly the prothrombotic effect) of progestagens.

The recognition of ESS as a hormone-sensitive disease is of clinical value in the recurrent setting. Estrogen receptors (ERs) and progesterone receptors (PRs) have been detected in ESS, both biochemically and immunohistochemically [11 –14]. PR positivity has resulted in a widely documented sensitivity of ESS towards progestagens [15 –23], whereas the presence of ERs enables aromatase inhibitors to exert an antitumoral effect [24].

Hormonal intake results in acceptable long-term outcomes, even in advanced stage disease [25]. The authors consider aggressive and repeated surgery (including secondary/tertiary debulking, thoracotomy and organ resection) in combination with the sequential use of hormones (progestins, gonadotrophin-releasing hormones and aromatase inhibitors) essential in the treatment of hormone-sensitive tumors with an indolent growth pattern. In the absence of hormone receptors, doxorubicin (50 mg/m²)–ifosfamide (5 g/m²)–Mesna (5 g/m²) has been successfully used [26]. The decrease in tumor size, the feasibility of resecting the iliac metastasis and the microscopic changes all suggested that the tumor was sensitive to doxorubicin–ifosfamide combination chemotherapy.

The presence of hormone receptors raises questions regarding the safety of hormone replacement therapy in women with a history of ESS. The largest clinicopathologic studies of ESS demonstrates that the biologic behavior of ESS is characterized by a recurrence rate of 36% and an indolent growth pattern [7]. This pattern enables concurrent conditions to interfere with its evolution. It was hypothesized that in vitro fertilization (IVF)-associated ovarian stimulation might adversely affect the otherwise indolent growth in ESS [25]. Furthermore, estrogen replacement therapy is contraindicated in women with ESS, since it was shown to have a detrimental effect [10]. In four out of five cases treated with estrogen replacement therapy, the disease recurred [10]. Given these characteristics of tumor biology and the availability of alternatives for estrogen replacement, including biphosphonates or raloxifen for the prevention of osteoporosis, venlafaxine for prevention of hot flushes and α-bisabolol-containing vaginal applications for the treatment of vaginal dryness, it is suggested that hormone replacement therapy is not prescribed in women with a hormone-sensitive tumor with a tendency to recur.

Uterine adenosarcoma

Uterine adenosarcomas (UASs) were first described by Clement and Scully in 1974 [27]. These rare neoplasms have a benign epithelial component, whereas the stromal component is typically of low grade. In 56% of cases, the sarcomatous component was ESS alone and, in an additional 9% of cases, a mixture of ESS and fibrosarcoma was present [28].

Since ESS is the predominant sarcomatous component in UAS and, given the suggested association of UAS with hyperestrogenism including exogenous estrogens [29], ovarian thecoma [29 –31] and Stein-Leventhal syndrome [28], the authors recently determined hormone receptor involvement in UAS [32,33]. The results suggest that the sarcomatous component of UAS expressed ERs and PRs in 16 of 20 (80%) and 12 of 20 cases (60%), respectively. In contrast, the sarcomatous component of UAS with sarcomatous overgrowth expressed ERs and PRs in zero of eight (0%) and one of eight cases (12%), respectively. The sarcomatous component of UAS without sarcomatous overgrowth expressed the ER and/or the PR in 18 of 20 (90%) cases. These findings put the reports on the use of toxic treatment modalities such as radiotherapy [34 –40] and chemotherapy [34,36 –38,40] in advanced or recurrent UAS in perspective. However, the observation that UAS with sarcomatous overgrowth rarely expresses hormone receptors suggests hormonal treatment to be of little value. Absence of hormone receptors is also in line with the observation that UAS with sarcomatous overgrowth are aggressive entities with a poor prognosis [35,41,42] that require aggressive treatment modalities. Treatment modalities should probably be applied as in UUS.

Given the frequent occurrence of ESS in the stromal component of UAS [28], many of the therapeutic options discussed for ESS can probably be extrapolated to UAS. Also, the biologic behavior of UAS resembles ESS, since a high recurrence rate (24%) and an indolent growth pattern have been observed in UAS [28], supporting an extrapolation of the data obtained in ESS.

Hormone-receptor positivity also raises questions regarding the safety of ovarian conservation in young women. Balancing the potential risks (recurrence) and benefits (e.g., preservation of reproductive function and avoidance of side effects of estrogen deprivation) of ovarian preservation is difficult due to the limited data and should be individualized. However, this discussion rarely occurs given the predominant occurrence of UAS in older women [28].

Since UAS frequently presents as a uterine polyp, the need for hysterectomy can be questioned. Although conflicting results appear in smaller series [34,37], in the largest series with clinical follow-up both myometrial invasion and sarcomatous overgrowth were related to an increased risk of recurrence [28]. Features that did not appear to be of prognostic value for the prediction of recurrence included age, stromal mitotic rate, size of the tumor, histologic grade of the sarcomatous component and presence of heterologous elements. Therefore, local excision may be considered in young patients in whom preservation of reproductive function is important, particularly if the tumor is pedunculated, the resection margin of the tumor is negative and sarcomatous overgrowth is absent [28].

Uterine leiomyosarcoma

Criteria for the diagnosis of uterine LMS have changed considerably during the last 10 years. Although an increased mitotic index and atypia were long considered the principal diagnostic criteria, the importance of coagulative tumor cell necrosis (CTCN) has now been generally accepted [1]. Currently, mitotic index, atypia and CTCN are used in combination to distinguish LMS from other smooth muscle cell tumors [43]. In the absence of CTCN and significant atypia, smooth muscle cell tumors with a high mitotic index are labeled as mitotically active LMSs. In the absence of CTCN and a high mitotic count, smooth muscle cell tumors with diffuse moderate-to-severe atypia are considered atypical LMSs with low risk of recurrence. An increased mitotic index or diffuse moderate atypia in combination with CTCN is classified as LMS. However, due to the limited experience with tumors lacking both significant atypia and an increased mitotic index but with CTCN, these are labeled uterine smooth muscle neoplasms (USMN) with low malignant potential (LMP), limited experience [43]. The recognition of different types of necrosis is also important to establish a diagnosis, and CTCN should be distinguished from hyaline and ulcerative necrosis [43]. In the most common type, hyaline necrosis [43 –45], the zone of necrosis is separated from viable tumor by a zone of connective tissue that varies from granulation tissue to hyalinized fibrous tissue depending on the age of the necrosis. The second type of necrosis, CTCN, is characterized by an abrupt transition from viable cells to necrotic cells without the interposed zone of granulation or fibrous tissue of infarct-type necrosis [43 –45]. Ulcerative necrosis typically involves the ulcerated surface of submucosal LMS [43,45]. Given the potential pitfalls in pathology and the rarity of these tumors, it is clear that an expert pathologist should be consulted in order to make an appropriate diagnosis.

A preoperative diagnosis in early stage LMS is unlikely to occur for two reasons. First, although endometrial biopsy is the gold standard for the diagnosis of endometrial pathology, it is unlikely to detect a mesenchymal uterine lesion unless endometrial involvement has occurred. Second, imaging studies fail to discriminate between benign and malignant uterine lesions in early stage disease. Ultrasound scanning is unable to reliably differentiate between fibroids and sarcomas, since no causes for concern were observed in several cases treated by gonadotropin-releasing hormone agonists who were subsequently diagnosed as having a sarcoma [46 –48]. However, in the presence of high diastolic blood flow and low impedance resulting from angiogenesis and neovascularization, it is expected that the multiparameter sonographic approach, which includes morphology, size (depicted by transvaginal ultrasonography) and color flow imaging with pulsed Doppler analysis of neovascular signals, can help in the diagnosis of uterine sarcoma. Vessels that may be measured include the uterine artery, intratumoral blood vessels and those feeding directly into the periphery of the tumor. Both the resistance index and peak systolic velocity are quantitative measures of intratumoral blood flow velocity waveforms. However, conflicting results have been published and no valid conclusions can be made [49 –51]. The absence of criteria for the diagnosis of LMS, retrospective analysis, lack of consensus on methodology and small series (only 27 sarcomas in three publications) contribute to these inconclusive results. Similar problems arise when resonance imaging is applied. In contrast, advanced stage disease is characterized by large volume disease, irregular borders and an infiltrative growth pattern and is more likely to be suspicious for malignancy on imaging.

Given the inconclusive results of clinical examination, endometrial biopsy and imaging studies in early stage disease (limited to the uterus), a hysterectomy is frequently applied without a pre-operative diagnosis. Small numbers are therefore preoperatively identified and subsequently referred to gynecologic oncologists.

Since adnexal or lymphatic spread is only present in advanced stage disease [52,53], simple hysterectomy is adequate in the surgical treatment of early stage uterine LMS. After surgery for this disease, there is no proven benefit of any adjuvant treatment. This evidence comes from the results of the only two randomized trials that are currently available investigating uterine sarcomas [54,55]. It should be noted; however, that both studies included all subtypes of uterine sarcomas, including LMS, CS and ESS, and the results of these two trials should be interpreted cautiously. The importance of adjuvant chemotherapy was first investigated almost 20 years ago. In a randomized trial of 156 women with early stage uterine sarcoma using doxorubicin or no further treatment, survival rates were comparable in both groups [54]. Recently, the results of a European Organization for the Research and Treatment of Cancer (EORTC) trial randomizing women with early stage uterine sarcoma to adjuvant radiotherapy or no further treatment were presented [55]. Survival curves were similar for both treatment arms, suggesting that radiotherapy is not beneficial in the adjuvant treatment of uterine sarcomas. Therefore, simple hysterectomy is the standard treatment for uterine LMS limited to the uterus and bilateral salpingo-oophorectomy is not necessary.

In recurrent disease or advanced stage disease, treatment is palliative only. Therapeutic options are limited and the administration of doxorubicin, epirubicin and ifosfamide result in response rates of 25, 31 and 17% [56 –58], respectively. The administration of a combination of cytotoxic drugs will result in better response rates, but the survival rates are similar at the cost of an increased toxicity. Therefore, single-agent therapy is frequently administered under these conditions. A recent report deserves special attention, since a remarkable response with an overall well-tolerated regimen was observed. Gemcitabine 900 mg/m² on days 1 and 8 plus docetaxel 100 mg/m² on day 8 resulted in an overall response rate of 53%. Seven patients had stable disease. Furthermore, 50% of patients previously treated with doxorubicin responded [59]. Other regimens have response rates lower than 11%. Currently, our knowledge of uterine LMS tumor biology is limited and newer treatment modalities are likely to take many years to become available.

Endometrial carcinosarcoma

Endometrial CS, also called malignant mixed Müllerian tumours (MMMT), are lesions that contain both carcinomatous and sarcomatous elements. The biphasic cellular population found in CS interested many researchers, who have focused on the question of whether this type of tumor originated from one (monoclonal theory) or two cell populations. A wide spectrum of methods have been proposed to answer this question. During the last 15 years, epidemiologic, clinicopathogic, immunohistologic, in vitro, in vivo and molecular genetic research have provided arguments to support the monoclonal nature of CS that pointed towards an endometrial origin. Recent textbooks therefore classify CS as a subtype of endometrial cancer [2]. Consequently, the designation endometrial CS corresponds best to its tissue origin and should be used instead of uterine CS. Depending on the mesenchymal cell type, the tumor is considered homologous or heterologous. In descending order, heterologous tumors contain one or more of the following elements: rhabdomyoblasts (rhabdomyosarcoma), cartilage (chondrosarcoma), osteoid bone (osteosarcoma), liposarcoma and melanocytes.

Surgery is the cornerstone of the treatment of endometrial CS and there is no proven benefit for any adjuvant treatment. Not only should surgery consist of hysterectomy and bilateral salpingo-oophorectomy, the tendency towards lymphatic and transperitoneal spread necessitates a comprehensive staging procedure [60]. A surgicopathologic analysis of 301 patients with endometrial CS revealed 18% lymph node positivity in apparent stage I–II disease [52]. The absence of information on the lymph node status results in similar treatment modalities for stage I–II and stage IIIc disease and is likely to effect the results of any study. Furthermore, similar to serous endometrial cancer, endometrial CS also portends a risk for transperitoneal spread, since positive peritoneal cytology [52,61,62], adnexal [52,62 –64] and omental/peritoneal [61,65] metastasis have been reported in 12–20, 12–28 and 9–47% of cases, respectively. It therefore seems logical to add cytology, peritoneal biopsies and infracolic omentectomy to the staging procedure in order to asses transperitoneal spread, similar to the staging procedure in ovarian cancer. Such a surgical staging resulted in the reassignation from stage I–II to stage III–IV in 61 of 301 (20%) of CS [52], and suggests staging procedures to be of diagnostic importance in endometrial CS. It should be noted that operative morbidity can be reduced, since the surgical requirements can be fulfilled using a laparoscopic procedure in experienced hands.

To describe the importance of surgical findings in clinical decision making regarding adjuvant treatment modalities, a parallel is made with serous endometrial cancer, another aggressive type of endometrial cancer with similar clinicopathologic characteristics. In the largest study of comprehensively surgically staged serous endometrial cancer, radiotherapy did not add to overall survival in node-negative stage I disease [66,67]. The absence of pelvic sidewall recurrences in comprehensively staged disease without further treatment might point towards a therapeutic role for lymphadenectomy [66]. The importance of adjuvant chemotherapy was investigated almost 20 years ago. A total of 156 women with early stage uterine sarcoma were randomized to doxorubicin or no further treatment, with survival rates comparable for both groups [54]. It should be noted; however, that both uterine LMS and endometrial CS were included. The incomplete surgical staging of CS results in a similar treatment for stage I–II and III disease and no subanalysis per stage is available. Both the inclusion of tumor types with different biologic behavior and the absence of comprehensive staging limit the clinical use of this study and newer studies should be evaluated. Although the clinical benefit of chemotherapy in endometrial CS remains unclear in incompletely staged disease [68], data in serous endometrial cancer suggest a benefit both in stage I–II [66] and in stage III–IV [69] disease. In a small series of incompletely staged endometrial CS, the combination of local control (radiotherapy) and systemic treatment resulted in a better outcome [62]. Nevertheless, the role of chemotherapy in endometrial CS needs to be confirmed per stage in prospective Phase II/III trials where comprehensive staging will be crucial to interpret the outcome.

In recurrent or advanced stage endometrial CS, a cure is no longer feasible and a palliative strategy balancing toxicity with activity should be applied. Cisplatin and ifosfamide are the cytotoxic drugs with the highest activity as single agents in endometrial CS, resulting in a response rate of 18–42 and 32%, respectively [70 –72]. The addition of cisplatin to ifosfamide offered a small improvement in progression-free survival over ifosfamide alone [73], but the added toxicity does not justify the use of this combination in settings where cure is no longer an option. Similarly, the combination of cisplatin–doxorubicin–ifosfamide in CS of the female genital tract resulted in a 56% response rate, with a complete response in 34%, but was associated with considerable toxicity [74]. Single-agent paclitaxel had only moderate activity, with 18% showing a response [75]. Interestingly, the combination of paclitaxel and carboplatin resulted in a complete response in four out of five patients [76]. The large experience of this combination in ovarian cancer demonstrates an acceptable toxicity and, although the number of cases is small [76], this combination clearly deserves further attention.

Executive summary

Endometrial stromal sarcoma (ESS)

The definition of ESS is considered best restricted to malignancies that were formally referred to as low-grade stromal sarcomas.

ESS is a hormone-sensitive disease in the vast majority of cases.

In early stage disease, hysterectomy and a bilateral salpingo-oophorectomy are performed.

In advanced or recurrent disease, aggressive and repeated surgery (including secondary/tertiary debulking, thoracotomy and organ resection) in combination with the sequential use of hormones (progestins, gonadotrophin-releasing hormones and aromatase inhibitors) are needed in the treatment of a hormone-sensitive tumor with indolent growth pattern.

Estrogen replacement therapy is contraindicated in women with endometrial stromal sarcoma.

Uterine adenosarcoma (UAS)

In the absence of valid data and given the frequent occurrence of ESS in the stromal component of UAS without sarcomatous overgrowth, many of the therapeutic options discussed for ESS can probably be extrapolated.

Leiomyosarcoma (LMS)

LMS is an aggressive disease entity with an overall survival of approximately 50% in early stage disease.

Metastatic spread is predominantly hematogenic.

Mitotic index, atypia and coagulative tumor cell necrosis are used in combination to distinguish leiomyosarcoma from other smooth muscle cell tumors.

In early stage disease, removal of the uterus is indicated. There is no survival benefit from adjuvant chemotherapy or radiotherapy.

In advanced stage disease, anthracyclines and ifosfamide are the most active cytotoxic agents.

In a palliative setting, the administration of a combination of cytotoxic drugs will result in better response rates, but the survival rates are similar at the cost of an increased toxicity. Therefore, single-agent therapy is frequently administered under these conditions.

A combination of gemcitabine and docetaxel resulted in a remarkable response.

Carcinosarcoma (CS)

Endometrial CS, also called malignant mixed Müllerian tumors, are lesions that contain both carcinomatous and sarcomatous elements.

CSs arise from epithelial tumors where metaplasia occurs.

The tendency for lymphatic and transperitoneal spread necessitates a comprehensive staging procedure including hysterectomy, bilateral salpingo-oophorectomy, omentectomy and pelvic node dissection.

There is no proven benefit from adjuvant chemotherapy or radiotherapy.

In recurrent or advanced stage endometrial carcinosarcoma, cure is no longer feasible. Cisplatin and ifosfamide are the cytotoxic drugs with the highest activity. Combinations of cytotoxic drugs will result in better response rates, but the survival rates are similar at the cost of an increased toxicity.

Paclitaxel and carboplatin resulted in a promising response rate and is associated with an acceptable toxicity, even in frail patients.

Undifferentiated sarcoma (UUS)

In early stage disease, removal of the uterus is indicated. There is probably no survival benefit from adjuvant chemotherapy or radiotherapy.

In advanced stage disease, doxorubicin and ifosfamide are the most active cytotoxic agents.

Future perspective

In early stage ESS, the clinical benefit from adjuvant progestins should be evaluated.

When a comprehensive staging procedure indicates early stage endometrial CS, the role of adjuvant chemotherapy needs to be investigated.

The role of taxanes in advanced stage or recurrent endometrial CS is promising, but should be confirmed in future trials.

The development of active agents for the treatment of LMS and UUS is needed.

Undifferentiated uterine sarcomas

Previously called high-grade ESS, this classification should now be abandoned, and currently these tumors are called UUS or poorly differentiated uterine sarcomas [6]. Several reports on the use of cytotoxic agents in uterine sarcomas have been published. However, most of these studies included a heterogeneous group of uterine sarcomas and the numbers were too small to draw conclusions from subgroups. Furthermore, in reports addressing chemosensitivity of endometrial stromal tumors, the distinction between what was formerly called low-grade ESS (currently called ESS) and high-grade ESS (currently called UUS or poorly differentiated uterine sarcomas) was not made. Nevertheless, some conclusions can be drawn and doxorubicin and ifosfamide appear to be the most active cytotoxic agents. Although numbers were low, in recurrent or metastatic ESS, response rates to doxorubicin and ifosfamide were 50 and 33%, respectively [9,77].

Conclusion

A summary of different approaches for different subtypes of uterine sarcomes is presented in Table 1. Distinction is made for early stage and advanced stage or recurrent disease. It is clear from this table that generalization of treatment modalities is not an option. Depending on the local experience, second opinion might be useful, both from a pathologic and clinical point of view.

Table 1.

Summary of the different therapeutic approaches for different subtypes of uterine sarcomas in early and advanced stage disease.

	Early stage disease (limited to uterus)
Sarcoma type	Surgery	Adjuvant
ESS	HT and BSO†	Progestins as part of a clinical trial
UAS*	HT and BSO†
LMS	HT
CS	HT, BSO, omentectomy, pelvic lymph node dissection	Platinum-based chemotherapy as part of a clinical trial
UUS	HT
	Advanced stage or recurrent disease
Sarcoma type	Surgery	Systemic
ESS	Debulking including organ resection	Progestins [15 –23] or aromatase inhibitors [24]
UAS*	Debulking including organ resection	Progestins or aromatase inhibitors
LMS		Anthracyclins [56,57] or docetaxel–gemcitabin [59]
CS		Platinum-based chemotherapy [70,71], paclitaxel–carboplatin [76]
UUS		Anthracyclins [9] or ifosfamide [77]

Without sarcomatous overgrowth

†

BSO can be omitted in young women.

BSO: Bilateral salpingo-oophorectomy; CS: Carcinosarcoma; ESS: Endometrial stromal sarcoma

HT: Hysterectomy; LMS: Leiomyosarcoma; UAS: Uterine adenosarcoma; UUS: Undifferentiated sarcoma.

Future perspective

Given the recognition that different uterine sarcomas encompass different entities, future studies should report on these malignancies separately in order to adequately draw conclusions. These studies should focus on the value of adjuvant hormonal treatment in ESS. Furthermore, the benefit of adjuvant cytotoxic treatment in early stage endometrial CS deserves further attention. In particular, taxanes are of interest, both in adjuvant and metastatic treatment of CS. Given the paucity of active agents for all subtypes, in particular for LMS and UUS, new compounds are urgently needed.

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Different Subtypes of Uterine Sarcoma Require a Separate Therapeutic Approach

Abstract

Keywords

Endometrial stromal sarcoma

Uterine adenosarcoma

Uterine leiomyosarcoma

Endometrial carcinosarcoma

Undifferentiated uterine sarcomas

Conclusion

Future perspective

References