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Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 489-494

Endometrial stromal sarcoma: Retrospective analysis of a tertiary care experience from India

Department of Radiation and Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Submission06-Mar-2020
Date of Decision27-May-2020
Date of Acceptance14-Jun-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Bhavana Rai
Department of Radiation Oncology, Post Graduate Institute of Medical Education and Research, Chandigarh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_70_20

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Background: Endometrial stromal tumors are rare tumors of mesenchymal origin, conventionally classified as low-grade and high-grade tumors based on the mitotic count.
Objective: In this study, our objective was to analyze the clinical characteristics and outcomes of patients with endometrial stromal sarcomas (ESS) treated at our institute.
Materials and Methods: Records of histologically proven cases of ESS treated at out institute between January 2011 and July 2015 were studied. The data were reviewed to ascertain the patient and disease characteristics and the treatment received before and after coming to the tertiary care hospital. Overall survival (OS) was assessed using the Kaplan–Meier method, and the differences were evaluated using the log-rank test.
Results: A total of 25 patients with ESS were identified, and the data for 23 of these were analyzed; 15 (65%) patients had low-grade tumors, and eight (35%) had high-grade tumors. About 53% of the patients with low-grade ESS (LG-ESS) had early stage disease, and 75% of those with high-grade ESS had Stage III/IV disease. All patients underwent at least a total abdominal hysterectomy. Adjuvant radiation and chemotherapy were given to 11 and 7 with LG-ESS and HG-ESS patients, respectively. Nine (39.1%) patients received hormonal therapy. Fifteen (65%) patients received some form of treatment before reporting at our institute. At the median follow-up of 22 months (range, 5–62 months), four patients died because of disease progression. The median OS for patients with high-grade tumors was 25 months; it was not reached for patients with low-grade tumors.
Conclusions: LG-ESS present at an earlier stage and have a better outcome than high-grade ESS, which receive more aggressive treatment. However, the general lack of awareness among practitioners has led to many patients not receiving standard treatment and counseling. Therefore, the treating oncologists must properly assess the risk management strategies before instituting treatment.

Keywords: Chemotherapy, endometrial stromal sarcoma, radiotherapy

How to cite this article:
Rattan R, Thakur P, Gupta A, Miriyala R, Ballari N, Rai B. Endometrial stromal sarcoma: Retrospective analysis of a tertiary care experience from India. Cancer Res Stat Treat 2020;3:489-94

How to cite this URL:
Rattan R, Thakur P, Gupta A, Miriyala R, Ballari N, Rai B. Endometrial stromal sarcoma: Retrospective analysis of a tertiary care experience from India. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 25];3:489-94. Available from: https://www.crstonline.com/text.asp?2020/3/3/489/295526

  Introduction Top

Uterine sarcomas are malignant tumors of the connective tissue elements in the endometrium and the myometrium. Compared to the more common epithelial endometrial carcinomas, sarcomas are considered more aggressive and have a poorer prognosis.[1] Endometrial stromal tumors are a rare subtype of uterine sarcomas affecting both premenopausal and postmenopausal women. They are the second most common pure mesenchymal tumors of the uterus. The World Health Organization has classified endometrial stromal tumors as endometrial stromal nodule (ESN), low-grade ESS (LG-ESS), high-grade ESS (HG-ESS), and undifferentiated uterine sarcoma, based on the tumor morphology, distinct chromosomal translocations, and prognosis.[2] However, in the recent times, a new molecular classification has emerged.[3],[4] The mainstay of treatment for ESS is surgery in the form of total abdominal hysterectomy with bilateral salpingooophoretomy (TAH-BSO). The roles of adjuvant chemotherapy and radiation are questionable, as there is mixed evidence with a lack of randomized controlled trials in this field.[5],[6],[7],[8] Prior to being referred to our tertiary care center, many patients are treated at different centers where knowledge about the disease is limited, which could prevent its early recognition. This in turn, can hinder the planning of the management of patients with ESS.

In this study, we performed a retrospective analysis of the data from patients with ESS who presented at our institute. Our aim was to evaluate the referred cases and assess the clinical outcome and behavior of ESS with respect to its clinicopathological grade and the impact of adjuvant therapy.

  Materials and Methods Top

General study details

This retrospective study was conducted in the department of radiotherapy and oncology at a tertiary care cancer institute in North India. The disease management group comprised a radiation oncologist, gynecologic surgeons, and a dedicated gynecologic pathologist. The requirement for obtaining a written informed consent for this analysis was waived by the Institutional Ethics Committee, as this was a retrospective departmental audit. The study was conducted in accordance with the various ethical guidelines as outlined in the declaration of Helsinki and the ICMR guidelines.


All consecutive histologically proven cases of ESS treated at our center between January 2011 and July 2015 were included in the analysis. Patients with incomplete treatment and follow-up details were excluded.


Our primary aim was to study the clinical course and outcomes of ESS with respect to its clinicopathological grade and the impact of adjuvant therapy.

Study methodology

Old records retrieved from paper-bound files and the computerized data from the Indian Council of Medical Research (ICMR) Hospital-Based Cancer Registry were reviewed for the identification of eligible patients. The paper-bound file for each patient was retrieved for data evaluation.

Diagnosis, staging, therapy, and follow-up

The gynecological cancers were reported by the Gynecology Pathology Department based on the results of routine histopathological staining and immunohistochemistry (IHC). Tumors were divided into two groups, namely LG-ESS and HG-ESS, based on the mitotic count. The LG-ESS were tumors with <10 mitoses/10 high-power fields (HPF), and the HG-ESS were those with more than 10 mitoses/10 HPF.[2]

IHC was done for all the patients. Based on the information obtained from the operative notes and pathology reports, the patients were staged according to the modification of the International Federation of Gynecology and Obstetrics staging system for endometrial cancer. As per this system, Stage I tumors are limited to the uterus; Stage II tumors extend beyond the uterus, but remain within the pelvis; Stage III tumors invade the abdominal tissues, including the pelvic and paraaortic nodes; and Stage IV tumors invade the rectum or bladder or metastasize distantly.[9] The decision to administer adjuvant therapy was based on the factors such as the tumor grade, incomplete surgery, residual disease, lymph node positivity, and metastatic disease. Hormone treatment was given to all the eligible patients whose tumors were hormone receptor positive. Patients were regularly followed up during and after the treatment with clinical examination and optional imaging, dictated by any clinical suspicion. Treatment toxicity was graded as per the common terminology criteria for adverse events, version 4.0 (U.S. Department of Health and Human Services, National Institutes of Health, National Cancer Institute). The database was locked in July 2016, and the data were reviewed to ascertain the patient and disease characteristics and the treatment received before and after coming to the tertiary care hospital.


As this was a retrospective analysis, we included all patients who fulfilled the inclusion and exclusion criteria of our study. There was no formal sample size calculation performed. Statistical analysis was performed using the Statistical Package for the Social Sciences (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp.). Descriptive statistics were used. The progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier method, and the differences were evaluated using the log-rank test.[10] PFS was defined as the time between the surgery and the onset of new symptoms, radiological progression, or death. OS was defined as the time from the diagnosis to the date of last follow-up or death due to any cause. A P-value of less than 0.05 was considered significant.

  Results Top

Patient characteristics

A total of 25 patients with ESS were identified. Of these, two patients were excluded from the analysis as one of them was lost to follow-up and the other did not complete the planned course of treatment. The data for the remaining 23 patients were analyzed. Of these, 15 patients had low-grade and 8 had high-grade tumors [Figure 1]. Majority (72%) of the patients in the low-grade group were postmenopausal. However, no such predilection was seen in the high-grade group, and an equal distribution of premenopausal and postmenopausal women (50%) was observed. The most common presenting symptoms were abnormal uterine bleeding and pain, and some patients had more than one symptom at presentation [Table 1].
Figure 1: Flow diagram of selection and analysis of patients with endometrial stromal sarcoma

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Table 1: Patient, tumor and treatment characteristics

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Tumor characteristics

Majority of the patients (53%) with LG-ESS had Stage I/II disease. On the other hand, most of the patients (75%) with HG-ESS had Stage III/IV disease. Histopathological details of the surgery were not available for one patient with LG-ESS presenting with peritoneal failure; thus, the patient could not be staged. The hormone receptor status was known for 18 patients. Estrogen receptor/progesterone receptor immunoreactivity was noted in eight low-grade and three high-grade tumors. Details of the tumor characteristics are provided in [Table 1].

Treatment characteristics

All patients underwent at least a TAH before any adjuvant treatment was initiated. Three out of five patients with high-grade tumors (60%) underwent an additional omentectomy/lymph node dissection, whereas only 3 out of 15 patients with low-grade tumors (20%) underwent an additional surgical procedure. The treatment related details are described in [Table 1]. Details of the patients who received prior initial treatment outside our tertiary care center are provided in [Table 2].
Table 2: Prior treatment received by patients before referral to our center

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A total of 14 (61%) patients received adjuvant therapy. Although for most cases the decision to administer adjuvant therapy was made by a multidisciplinary tumor board comprising the gynecology, oncology, and pathology teams (including the cases that were referred to our institute after some initial treatment outside), for few cases the treatment was instituted at the discretion of the treating oncologist. The general guide to deciding whether adjuvant treatment should be administered was to follow a conservative approach for the low-grade tumors, where adjuvant radiation was administered only when an extrauterine spread of the disease was suspected. More aggressive therapy was reserved for high-grade tumors, where both chemotherapy and radiation therapy were offered and discussed with patients as treatment options. Any residual disease not feasible to be covered within radiation portals was managed with chemotherapy, even for a low-grade tumor.

Seven patients received adjuvant chemotherapy. Of these, five were given ifosfamide and doxorubicin combination chemotherapy (including the one patient with LG-ESS) and two received paclitaxel and carboplatin. All but one patient completed six cycles of chemotherapy. One patient received five cycles of chemotherapy and refused further chemotherapy because of logistic reasons. No grade 3 toxicity was seen. Nine patients (8 LG and 1 HG ESS) received hormonal therapy. Letrozole was given to seven patients, and two patients received tamoxifen.

Eleven patients received whole pelvic radiation, with the dose ranging from 4600 to 5000 cGy at 1.8–2 Gy/fraction. All patients received radiation by three-dimensional conformal radiotherapy. No grade 3 toxicity was noted.

Survival outcomes

At the median follow-up of 22 months (5–62 months), two patients were lost to follow-up and four patients (two of each grade) had died. All patients who died had progressive loco-regional metastasis to the omentum, and one patient had additional distant visceral metastasis to the lung. The median PFS was 8.5 months (95% confidence interval [CI], 7.5–19.7). The median OS was not reached for the low-grade tumors. The median OS for the high-grade tumors was 25 months (95% CI, 8.5–29.4). [Figure 2] depicts the Kaplan–Meir curves for the OS of patients with high- and low-grade tumors. The difference in the OS was not significant between the two groups (P = 0.305).
Figure 2: Kaplan-Meier survival curves of patients with high- and low-grade endometrial stromal sarcomas

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No definitive salvage therapy was instituted at the time of relapse due to the poor performance status. All patients were given symptomatic and supportive treatment in our palliative care clinic.

  Discussion Top

In this study, we have attempted to shed some light on the practices and treatment approach of the oncologists dealing with ESS in our institute as well as in other centers. We found that HG-ESS are aggressive tumors with a higher stage at presentation and an aggressive clinical course. In contrast, for LG-ESS, though the stage at presentation was often lower (Stage I/II were 53.3%), a significant proportion of the patients had Stage II/III disease (39.9%).

Similar observations were made by Gadducci et al. in their multicenter analysis of data from 66 patients with ESS.[11] In this analysis, the authors have described the patient characteristics, along with the recurrence and survival patterns. Our results are in line with their reported outcomes. However, ours is the first study to include a real-world experience, wherein the practices of community oncologists before the patients' referral to a tertiary care center have been elucidated.

In our retrospective analysis, all the patients were seen at our clinic after a postsurgery histopathological diagnosis of ESS had been made. Patients had undergone a minimum of TAH-BSO before they were taken up for adjuvant treatment. Surgeons favored a more extensive treatment approach for high-grade tumors, where 60% of the patients underwent an additional omentectomy/lymph node dissection, in comparison to the low-grade tumors, where only 20% underwent additional surgical procedures. Sixty-five percent of the patients had received initial treatment outside. The different treatment modalities such as myomectomy and chemotherapy were likely used for fertility preservation. However, owing to the retrospective nature of our study, conclusions could not be drawn in this regard.

The type of surgery required for patients with ESS still remains debatable. However, considering the number of patients in our cohort who developed peritoneal failures (17%), it appears that peritoneal biopsy or omentectomy along with routine surgical procedure may have some value. In the study by Gadducci et al., as mentioned earlier, 66% of the failures were seen in the pelvis and peritoneum.

Overall, 47.8% of the patients received postoperative radiotherapy (47% of patients in the low-grade group and 50% in the high-grade group). The whole-pelvic radiation doses were consistent at 5000 cGy in 25 fractions for 5 weeks.

In a more recent retrospective review of 131 patients with ESS, Bodner et al. reported a 5-year OS rate of 62%.[12] In this study, the decision to administer adjuvant therapy was made by the treating physician. Disease recurrence developed in 10 (50%) out of 20 patients who received adjuvant radiation, and 3 (60%) out of 5 patients who received adjuvant chemotherapy. Fourteen patients developed recurrent disease, and their median disease-free survival was 11 months (range 5–60). The authors concluded that an early tumor stage, low myometrial invasion, and low mitotic count were associated with a higher OS in patients with ESS.[12] Considering that most of the data on ESS come from retrospective case reviews and the individual variations in treatments, there is a lack of clarity in terms of the indications and the use of adjuvant therapy.

In our study, 30% of the patients received adjuvant chemotherapy consisting of an anthracycline-based regimen. Of the two patients with low-grade tumors, whose residual disease was beyond the coverage of the radiation portals, one patient received chemotherapy and the other opted for palliative care only; both the patients had hormone receptor negative tumors. The choice of ifosfamide and doxorubicin-based chemotherapy in our department has been extrapolated from the usage of these compounds in the management of sarcomas of other regions. There are data from phase II trials regarding the use of chemotherapy with drugs, including those used in soft-tissue sarcomas of other sites such as adriamycin, ifosfamide, dacarbazine, vinorelbine, gemcitabine, docetaxel, and temozolomide.[13] The Gynecologic Oncology Group study included 31 patients with ESS, with primary advanced or recurrent disease. Overall, 33% of the patients responded to ifosfamide at a dose of 1.5 g/m2 given on days 1–5, every 3 weeks; complete and partial remission rates of 14% and 19%, were observed, respectively. The median PFS of the entire group was 3 months.[14]

An important aspect that was highlighted by our study was the lack of awareness about the type of tumor and the optimum treatment among the practitioners who first treated the patients outside the tertiary care center. This may be, in part, due to the rarity and lack of consensus guidelines for this group of diseases. For two patients, a myomectomy was performed by outside surgeons with the intent of preserving the fertility; this shows the lack of knowledge among the non-oncologic surgeons, when dealing with a supposedly rare tumor like ESS. These two patients later underwent complete surgery. A repeat surgery, however, is not possible in every case, and this can lead to an adverse effect on the survival.

Our study is one of the only studies on ESS from India, and it can help to improve our knowledge about this rare tumor. It highlights the discrepancies in the treatment of ESS in the various community centers, which may be associated with the lack of knowledge among clinicians and pathologists regarding its early identification and treatment. However, the study has several limitations. This is a retrospective analysis and serves only to identify the practices of treatment of ESS in a tertiary care hospital and the various scenarios that oncologists encounter while dealing with patients on a case-to-case basis. For all histopathologically diagnosed cases of ESS, the hormone receptor status was determined solely on the basis of IHC. Molecular studies were not performed. The follow-up period was short, and the survival data were premature for the low-grade tumors.

  Conclusion Top

ESS comes in a wide spectrum of clinical and histopathological varieties. Low-grade tumors present at an earlier stage than their high-grade counterparts. At our institute, we favor an aggressive treatment strategy for high-grade tumors with the routine use of adjuvant radiation and chemotherapy. Rare gynecological malignancies like ESS need a proper staging surgery and appropriate risk stratification before initiating the treatment.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Ferreira J, Félix A, Lennerz JK, Oliva E. Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Arch 2018;473:665-78.  Back to cited text no. 3
Norris HJ, Taylor HB. Mesenchymal tumors of the uterus. I. A clinical and pathological study of 53 endometrial stromal tumors. Cancer 1966;19:755-66.  Back to cited text no. 4
Berchuck A, Rubin SC, Hoskins WJ, Saigo PE, Pierce VK, Lewis JL Jr. Treatment of endometrial stromal tumors. Gynecol Oncol 1990;36:60-5.  Back to cited text no. 5
Weitmann HD, Knocke TH, Kucera H, Pötter R. Radiation therapy in the treatment of endometrial stromal sarcoma. Int J Radiat Oncol Biol Phys 2001;49:739-48.  Back to cited text no. 6
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Rauh-Hain JA, del Carmen MG. Endometrial stromal sarcoma: A systematic review. Obstet Gynecol 2013;122:676-83.  Back to cited text no. 8
International Federation of Gynecology and Obstetrics. Annual Report on the Treatment in Gynecologic Cancer. Stockholm: International Federation of Gynecology and Obstetrics; 2009. p. 19.  Back to cited text no. 9
Chakraborty S. A step-wise guide to performing survival analysis. Cancer Res Stat Treat 2018;1:41-5.  Back to cited text no. 10
  [Full text]  
Gadducci A, Sartori E, Landoni F, Zola P, Maggino T, Urgesi A, et al. Endometrial stromal sarcoma: Analysis of treatment failures and survival. Gynecol Oncol 1996;63:247-53.  Back to cited text no. 11
Bodner K, Bodner-Adler B, Obermair A, Windbichler G, Petru E, Mayerhofer S, et al. Prognostic parameters in endometrial stromal sarcoma: A clinicopathologic study in 31 patients. Gynecol Oncol 2001;81:160-5.  Back to cited text no. 12
Serkies K, Pawłowska E, Jassem J. Systemic therapy for endometrial stromal sarcomas: Current treatment options. Ginekol Pol 2016;87:594-7.  Back to cited text no. 13
Sutton G, Blessing JA, Park R. Ifosfamide treatment of recurrent or metastatic endometrial stromal sarcomas previously unexposed to chemotherapy: A study of the Gynecologic Oncology Group. Obstet Gynecol 1996;87:747-50.  Back to cited text no. 14


  [Figure 1], [Figure 2]

  [Table 1], [Table 2]


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