Original Article
Ovarian preservation for low-grade
►► Additional material is
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1
Division of Gynecologic
Oncology, University of
Pennsylvania Health System,
Philadelphia, Pennsylvania, USA
2
Surgery Working Group,
Obstetrics and Gynecology
Subgroup, Society of Junior
Doctors, Athens, Greece
Correspondence to
Dimitrios Nasioudis , Division
of Gynecologic Oncology,
Department of Obstetrics and
Gynecology, Hospital of the
University of Pennsylvania,
Philadelphia, PA 19104, USA; ​
dimitrios.​nasioudis@​uphs.​
upenn.​edu
Received 29 June 2018
Revised 15 October 2018
Accepted 26 October 2018
© IGCS and ESGO 2019. No
commercial re-use. See rights
and permissions. Published by
BMJ.
To cite: Nasioudis D, Ko EM,
Kolovos G, et al. Int J Gynecol
Cancer 2019;29:126–132.
126
endometrial stromal sarcoma: a systematic
review of the literature and meta-analysis
Dimitrios Nasioudis,1,2 Emily M Ko,1 Georgios Kolovos,2 Stylianos Vagios,2 Dimitrios Kalliouris,2
Robert L Giuntoli1
HIGHLIGHTS
• Approximately one in four patients with low-grade endometrial stromal sarcoma are managed with ovarian preservation.
• Ovarian preservation is associated with an increased risk of tumor relapse.
• Based on limited evidence, it may not result in an increased risk of death.
Abstract
Objective  To evaluate the effect of ovarian preservation
on oncologic outcomes for women with low-grade
endometrial stromal sarcoma of the uterus.
Methods  A systematic search of the Medline, Embase,
Cohrane, and Web of Science databases was performed
based on the Preferred Reporting Items for Systematic
Reviews and Meta-analyses guidelines . Studies including
patients with low-grade endometrial stromal sarcoma
who had hysterectomy were identified. Data on tumor
recurrence and death rate were pooled using a random
effects model.
Results  A total of 17 studies met the inclusion criteria
and reported on 786 patients. Based on available
information, ovarian preservation was noted in 190
patients while 501 had bilateral salpingo-oophorectomy. A
significantly increased tumor recurrence rate was observed
in the ovarian preservation group (89/190, 46.8%)
compared with the bilateral salpingo-oophorectomy group
(121/501, 24.2%) (OR 2.70, 95% CI 1.39 to 5.28). Based
on data from 162 patients, no difference in death rate was
noted between the ovarian preservation (2/34, 5.9%) and
bilateral salpingo-oophorectomy (9/128, 7%) groups (OR
0.80, 95% CI 0.18 to 3.47).
Conclusions  Approximately one-quarter of patients with
low-grade endometrial stromal sarcoma were managed
with ovarian preservation. These women experienced
a higher recurrence rate. Hormone exposure may be
responsible for this elevated risk. Given the apparent high
salvage rate, however, ovarian preservation may be an
option only in a well-informed patient population.
Introduction
Uterine sarcoma is a rare group of tumors arising from
mesenchymal cells and represents approximately
3% of all uterine cancers.1 Low-grade endometrial
stromal sarcoma is the second most prevalent uterine
sarcoma. Microscopically it consists of well-differ-
entiated endometrial stromal cells with mild nuclear
atypia.1 On presentation, low-grade endometrial
stromal sarcoma is typically confined to the uterus
Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063
Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000063 on 7 January 2019. Downloaded from http://ijgc.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
and exhibits an indolent behavior.2 Five- and 10-year
survival rates above 90% have been reported for
women with stage I disease.3 4
Surgical management of low-grade endometrial
stromal sarcoma includes hysterectomy with or
without bilateral salpingo-oophorectomy. The value
of lymphadenectomy and adjuvant treatment has yet
to be established.2 Low-grade endometrial stromal
sarcoma tumors consistently express estrogen and
progesterone receptors. Therefore, bilateral salpin-
go-oophorectomy serves to remove occult ovarian
micrometastases and also eliminates the endog-
enous production of hormones that may stimulate
tumor growth.5 As more than half of women diag-
nosed with low-grade endometrial stromal sarcoma
are pre-menopausal, however, surgical menopause
may have long-term implications.1 To date, only small
retrospective studies have evaluated the safety of
ovarian preservation in women with low-grade endo-
metrial stromal sarcoma, often reaching opposite
results, making their use for the basis of manage-
ment recommendations challenging.3–21 In contrast,
the safety of ovarian preservation in pre-menopausal
women with International Federation of Gynecology
and Obstetrics grade I endometrioid adenocarcinoma
of the endometrium, another hormonally responsive
tumor, has been extensively evaluated and is currently
offered to carefully selected patients.22 23
The aim of this comprehensive systematic review
and meta-analysis is to determine the effect of
ovarian preservation compared with bilateral salpin-
go-oophorectomy in women with low-grade endome-
trial stromal sarcoma on oncologic outcome.
Methods
Search strategy
This systematic review was conducted in accordance
with the Preferred Reporting Items for Systematic

Review and Meta-Analyses guidelines24; a protocol was deter-
mined beforehand by participating authors. The present study was
registered with the PROSPERO Registry with the unique identifying
number CRD42018082378.
A comprehensive electronic search from January 1, 1970 to
May 28, 2018 of Pubmed/Medline, EMBASE, Cochrane, and Web
of Science databases was performed with the use of the following
keywords: “(Uterus or Uterine) AND ((endometrial stromal sarcoma)
OR (stromal sarcoma) OR ESS)”. In addition, all references of
included studies were systematically hand-searched.
Eligibility of studies
Our investigation was limited to complete articles available in the
English language. Inclusion criteria were: (1) studies on women
with low-grade endometrial stromal sarcoma who had hysterec-
tomy; (2) studies with at least five cases; (3) studies providing data
on the performance of oophorectomy; and (4) studies with data
on recurrence rate and/or overall survival. Exclusion criteria were:
(1) studies on high-grade or undifferentiated endometrial stromal
sarcoma; (2) studies reporting on all histologic subtypes of uterine
sarcoma; (3) studies on women who had morcellation of incidental
sarcomas; (4) database-based, overlapping, or republished studies;
(5) studies on fertility-preserving surgery or patients who did not
undergo hysterectomy; and (6) studies in which the number of
events (deaths or recurrences) could not be calculated from the
reported data.
Data extraction
The methodological quality of the studies was assessed using the
Newcastle–Ottawa Quality Assessment Scale for non-randomized
studies.25 From each eligible study the following parameters were
extracted when applicable: general study characteristics (author,
country of origin, date of publication, years of recruitment), patient
demographics (age, percentage of pre-menopausal women, race),
performance of lymphadenectomy, adjuvant treatment (radia-
tion therapy, chemotherapy, hormonal therapy), recurrence, and
death rate. If the required data for the pooled analysis (ie, number
of events) were not readily available in the published articles, the
corresponding authors were contacted. In our study we defined
hormone replacement as the use of estrogen with or without
progesterone to replace hormones lost by bilateral salpingo-oo-
phorectomy and hormone therapy as the use of selective estrogen
receptor modulators, aromatase inhibitors, and/or progestins to
treat the neoplastic process.
Synthesis of data
The level of statistical heterogeneity was evaluated with the I2
statistic. A random effects model was used to compare outcomes
between the two groups and OR and 95% CI were calculated with
the DerSimonian and Laird approach. Forest plots were created for
each comparison while graphical funnel plots were generated to
determine the presence of publication bias by visual inspection.
P values <0.05 were considered statistically significant. If signifi-
cant heterogeneity was noted, a sensitivity analysis was performed
by the sequential omission of each study. Statistical analysis was
performed with the Cochrane Review software (Review Manager
version 5.2).26 The present study was exempt from Institutional
Board Review.
Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063
Original Article
Results
Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000063 on 7 January 2019. Downloaded from http://ijgc.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
A total of 17 studies reporting on 786 patients met the inclusion
criteria.3 5–20 Supplemental figure 1 depicts the PRISMA flow
diagram of the search strategy. All studies were retrospective in
nature and consisted of 16 cohort studies and one case-control
study. The majority originated from North America (eight studies)
followed by Asia (five studies) and Europe (four studies). No publi-
cation bias was present as assessed by funnel plots.
Median age at diagnosis ranged from 41 to 51 years. Approxi-
mately one-third (33.2%, 240/722) underwent lymphadenectomy
during their staging procedure. Most patients had stage I disease,
(74.9%, 472/630). Adjuvant radiation therapy and chemotherapy
were administered to 16.6% (113/679) and 21.4% (145/679) of
women respectively. Adjuvant hormonal treatment was employed in
the management of 20.9% (142/679) of patients. Table 1 summa-
rizes the demographic and clinicopathological characteristics of the
included studies.
Seventeen studies provided information on the tumor recurrence
rate and included 190 women in the ovarian preservation group
and 501 women in the bilateral salpingo-oophorectomy group.
There was moderate heterogeneity among the included studies
(p=0.01, I2=49%). A total of 89/190 (46.8%) women in the ovarian
preservation group experienced a tumor recurrence compared with
121/501 (24.2%) in the bilateral salpingo-oophorectomy group.
Based on the random effects model, there was an increased risk of
tumor recurrence in the ovarian preservation group (OR 2.70, 95%
CI 1.39 to 5.28) (Figure 1). A sensitivity analysis was performed by
excluding one study at each time with no change in the final results.
Three studies provided information on the death rate among
women with low-grade endometrial stromal sarcoma, which
included 34 women in the ovarian preservation group and 128
women in the bilateral salpingo-oophorectomy group. There was no
heterogeneity among the included studies (p=0.69, I2=0%). A total
of two (5.9%) and nine (7.0%) deaths were observed in the ovarian
preservation and bilateral salpingo-oophorectomy groups, respec-
tively. Based on the random effects model, there was no statistically
significant difference in the risk of death between women in the
ovarian preservation and bilateral salpingo-oophorectomy groups
(OR 0.80, 95% CI 0.18 to 3.47) (Figure 2).
Seven studies provided data on tumor recurrence exclusively
among pre-menopausal women and included 91 in the ovarian
preservation group and 87 women in the bilateral salpingo-oopho-
rectomy group. There was low heterogeneity among the included
studies (p=0.23, I2=28%). A total of 29/91 (31.9%) women in
the ovarian preservation group experienced a tumor recurrence
compared with 20/87 (23%) in the bilateral salpingo-oophorectomy
group. Based on the random effects model, there was no statis-
tically significant difference in recurrence risk between the the
ovarian preservation group and the bilateral salpingo-oophorec-
tomy group (OR 1.38, 95% CI 0.55 to 3.50) (Figure 3).
Eight studies provided data on tumor recurrence among patients
with early stage disease (stage I–II) and included 45 women in
the ovarian preservation group and 151 in the bilateral salp-
ingo-oophorectomy group. There was moderate heterogeneity
among the included studies (p=0.01, I2=62%). A total of 15/45
(33.3%) women in the ovarian preservation group experienced a
tumor recurrence compared with 25/151 (16.6%) in the bilateral
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Original Article

Table 1  Demographic and clinicopathological characteristics of included studies

Stage
Median age, years* Median follow-up,
First author Year Country Institution Years recruiting N (range) PMP I II III IV LND RT CT HT months* (range)

Agarwal et al6 2017 India Amrita Institute of Medical 2005–2016 28 N/A N/A N/A N/A N/A N/A N/A N/A
Sciences
Amant et al7 2007 Belgium Katholieke University 1986–2005 31 44 (18–60) 81% 22 0 4 5 6 0 0 7 N/A
Leuven
Beck et al8 2012 USA Cleveland Clinic, Roswell 1986–2002 42 44.8 (27–73) N/A 28 1 8 3 9 5 4 14 130
Park, Magee
Berchuck et al9 1990 USA Memorial Sloan Kettering 1970–1984 22 48 N/A 19 1 2 0 0 3 3 0 N/A
Cheng et al10 2011 USA MD Anderson 1995–2006 74 43.5 (22–68) 82% N/A 18 9 3 27 76 (2–444)
Chu et al11 2003 USA Yale Universtity 1978–2003 22 45.5 (19–76) 72.7% 17 0 4 1 7 1 0 13 100 (2–258)
Evans et al12 1982 USA MD Anderson N/A 11 39 (20–60) 91% 7 2 0 2 0 8 2 1 N/A
Feng et al14 2011 China Fudan University 1992–2007 57 43 (19-63) N/A 45 12 0 0 36 6 47 0 68 (17–140)
Gaducci et al15 1996 Italy Mutlicenter (Italy) 1980–1994 26 44 (18–68) N/A 19 1 4 2 7 4 5 1 92 (4–167)
Huang et al16 1996 Taiwan National Taiwan University 1965–1994 17 43.5 (24–75) 85% 7 0 8 2 1 4 1 10 48.1 (15–173)
Li et al5 2005 USA Johns Hopkins, UCLA, n/a 36 46 (26–50) for OP, 80.5% 36 0 0 0 N/A 4 0 8 34.8 for ovarian
UTSW, Jefferson 45 (25–59) for preservation and 60
bilateral salpingo- for bilateral salpingo-
oophorectomy oophorectomy
Malouf et al13 2009 France Institut Gustav 1977–2007 54 47 (25–73) 76% 48 6 0 0 4 14 3 10 58 (3–348)
19
Mansi et al 1990 UK Royal Marsden Hospital 1973–1987 8 37 (30–50) 75% 6 0 1 1 0 3 0 0 45 (8–128)
Norris et al20 1966 USA Armed Forces Database N/A 18 N/A N/A N/A N/A N/A N/A N/A N/A
Stewart et al18 2018 USA University of Washington 1985–2014 112 48.5 (22–87) N/A 49 8 20 36 4* 1* 28* 55 (1–325)
Yoon et al3 2013 South Samsung Medical Center, 1990–2012 114 45 (18–74) 77.2% 92 9 4 9 45 12 20 12 46 (0.5–251)
Korea Asan Medical Center
Zhou et al17 2015 China Xiamen Cancer Center 1991–2013 114 41 (19–58) 86% 77 12 22 3 71 36 56 11 40 (3–172)
Total 1965–2013 786 472 53 105 240 113 145 142

BOLD: mean,
*Information on adjuvant treatment available for 51 patients.
CT, Chemotherapy; HT, hormonal therapy; LND, lymphadenectomy; PMP, premenopausal; RT, radiation therapy.

Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063

Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000063 on 7 January 2019. Downloaded from http://ijgc.bmj.com/ on 2 April 2019 by guest. Protected by copyright.

Figure 1  Forest plot of pooled recurrence rate in patients with low-grade endometrial stromal sarcoma who had ovarian
preservation (OP) or bilateral salpingo-oophorectomy (BSO).
salpingo-oophorectomy group. Based on the random effects model,
there was a no statistically significant difference in tumor relapse
risk between the two groups (OR 2.69, 95% CI 0.55 to 13.50)
(Figure 4).
Seven studies provided data on tumor recurrence stratified by the
administration of adjuvant hormonal therapy (92 and 225 patients
in the hormonal therapy and non-hormonal therapy groups, respec-
tively). There was no heterogeneity among the included studies
(p=0.76, I2=0%). A total of 23/92 (25%) women in the hormonal
therapy group had a tumor relapse compared with 79/225 (35.1%)
in the non-hormonal therapy group. Based on the random effects
model, there was a decreased risk of tumor recurrence in the
hormonal therapy group (OR 0.41, 95% CI 0.21 to 0.78) (Figure 5).
Discussion
The removal of ovaries achieves resection of possible subclinical
ovarian metastases and induces surgical menopause in patients
with a hormonally responsive tumor. Data supporting bilateral
salpingo-oophorectomy for women with low-grade endometrial
stromal sarcoma, however, are limited.21 Although several inves-
tigations suggest that the prevalence of occult ovarian metastases
for low-grade endometrioid adenocarcinoma of the endometrium
Figure 2  Forest plot of pooled death rate in patients with low-grade endometrial stromal sarcoma who had ovarian
preservation (OP) or bilateral salpingo-oophorectomy (BSO).
Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063
Original Article
Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000063 on 7 January 2019. Downloaded from http://ijgc.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
appears to be small,22 23 only limited data addressing this ques-
tion for low-grade endometrial stromal sarcoma are available.
Dos Santos et al reported no occult ovarian metastases among 20
patients with disease grossly confined to the uterus and grossly
normal ovaries.27 Further studies are warranted since the majority
of women present with apparent early stage disease.
Low-grade endometrial stromal sarcoma consistently expresses
steroid hormone receptors and is considered a hormone sensitive
tumor. Online supplementary table 1 summarizes published studies
examining the expression of estrogen and progesterone receptor
in low-grade endometrial stromal sarcoma; cumulative rates of
estrogen receptor and progesterone receptor positivity were 76%
and 81.2%, respectively.28–45 Removal of the ovaries results in loss
of endogenous hormone production that could theoretically stimu-
late growth of residual tumor cells.
Existing retrospective studies investigating the safety of ovarian
preservation individually present conflicting results.3–21 The lack of
conclusive evidence is reflected in the discrepancies among major
cooperative group guidelines. The National Comprehensive Cancer
Network clinical practice guidelines suggest that providers should
consider re-resection of the ovaries for patients with low-grade
endometrial stromal sarcoma.46 However, the Gynecologic Cancer
InterGroup recommendations state that ovarian preservation could
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Original Article
Figure 3  Forest plot of pooled recurrence rate in pre-menopausal patients with low-grade endometrial stromal sarcoma who
had ovarian preservation (OP) or bilateral salpingo-oophorectomy (BSO).
be offered to young women with small tumors. In addition, the
recently updated European Society of Medical Oncology guidelines
conclude that the value of bilateral salpingo-oophorectomy is not
established, particularly for pre-menopausal women.47
In our meta-analysis, women with preserved ovaries had a
significantly increased risk of tumor relapse. After excluding
studies without menopausal status, a trend towards an increased
risk of relapse was also noted when the analysis was limited to the
178 known pre-menopausal women (from an initial cohort of 673
patients). The lack of statistical significance in this difference in the
subset analysis is likely due to the limited number of subjects.
Only three studies reported death rates for low-grade endometrial
stromal sarcoma. While ovarian preservation was associated with an
increased risk of recurrence in our meta-analysis, no difference in
death rate was observed between women who did and did not undergo
bilateral salpingo-oophorectomy. Median follow-up ranging from 40 to
115 months does not appear to be an issue.7 16 17 Our recent analysis
of the Surveillance, Epidemiology, and End Results database found
similar results, with no difference in overall survival between women
aged <50 who did (n=369) and did not (n=151) undergo bilateral
salpingo-oophorectomy.21 After a median follow-up of 116 months,
36 (6.7%) deaths were observed from which only 13 (36%; 2.4% of
the total population) were attributed to the tumor.21 However, lack of
central pathology review is a limitation of that study. Previous anal-
yses of the Surveillance, Epidemiology, and End Results dataset also
did not detect any survival difference between patients managed with
bilateral salpingo-oophorectomy or with ovarian preservation.48 49 We
Figure 4  Forest plot of pooled recurrence rate in patients with stage I-II low-grade endometrial stromal sarcoma who had
ovarian preservation (OP) or bilateral salpingo-oophorectomy (BSO).
130
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hypothesize that a high salvage rate with hormonal therapy and/or
bilateral salpingo-oophorectomy (secondary cytoreduction) in patients
with recurrence may be responsible for the lack of survival difference.
Recurrence in patients with low-grade endometrial stromal
sarcoma may be treated with secondary cytoreduction, oophorec-
tomy, and administration of hormonal therapy. Complete secondary
cytoreduction of recurrent disease correlates with survival. Bai et
al reported 5-year survival rates following relapse for women with
(n=15) and without (n=34) macroscopic residual tumor after salvage
surgery of 65% and 100%, respectively (p<0.001).4 None of the
patients with locally recurrent disease died of their disease.4 Simi-
larly, Yoon et al reported that performance of secondary cytoreduc-
tive resection was independently associated with better survival in a
group of 33 patients with recurrent low-grade endometrial stromal
sarcoma.3 Hormonal management also appears to be successful in
the management of recurrence. Cheng et al reported that, among 24
patients with recurrent low-grade endometrial stromal sarcoma who
received hormonal therapy, 17% and 10% had complete and partial
response, respectively, while 53% had stable disease.10 In 11 patients
with recurrent or residual disease, an objective response to hormonal
treatment was observed in nine (82%) patients.50 A response rate of
88% to progestin therapy was reported by Chu et al in eight women
with recurrent low-grade endometrial stromal sarcoma.11 Aromatase
inhibitors also represent an attractive option with a response rate of
77.4% in a review of data from 30 patients.51 Optimal agents and
dosage are yet to be established. Despite the limitations, these find-
ings seem to indicate that low-grade endometrial stromal sarcoma
Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063

Figure 5  . Forest plot of pooled recurrence rate in patients with low-grade endometrial stromal sarcoma stratified by
administration of adjuvant hormonal therapy.
recurrences can potentially be salvaged, especially if localized. Online
supplementary table 2 summarizes the location of tumor relapse in
the included studies. Unfortunately only one study provided informa-
tion on the pattern of recurrence based on the preservation or other-
wise of ovaries. Li et al5 provided information on the location of tumor
relapse among patients who underwent ovarian preservation or bilat-
eral salpingo-oophorectomy. They did not indentify any differences in
the pattern of recurrence between the two groups.5
The increased risk of recurrence for patients with low-grade endo-
metrial stromal sarcoma managed with ovarian preservation suggests
a hormonal mechanism. Ovarian preservation could allow stimulation
of otherwise undetectable hormonally responsive tumor cells. However,
as studies included in this analysis were retrospective, non-hormonal
confounding factors could be responsible for the findings. At best,
the efficacy of adjuvant hormonal treatment is mixed. Three inves-
tigations with small patient populations suggest an advantage to
adjuvant hormonal treatment. Malouf et al did not observe any recur-
rence in a group of 10 women with early stage low-grade endome-
trial stromal sarcoma who received adjuvant hormonal treatment.13 In
addition, Beck et al observed a trend towards a decreased recurrence
rate among women (n=42) with early stage low-grade endometrial
stromal sarcoma who received adjuvant hormonal therapy (14.3%
vs 38.5%, p=0.26).8 Similarly, Chu et al reported a lower recurrence
rate among women (n=22) who received adjuvant progestin therapy
(31% vs 67%).11 In contrast, larger cohort studies (n>100) have
failed to confirm a benefit for adjuvant hormonal treatment.3 17 These
discrepancies may be due to the heterogeneity of the regimens used;
medroxyprogesterone acetate, megestrol acetate, aromatase inhibi-
tors, mifepristone, and gonadotropin-releasing hormone analogs have
all been employed in different dosages. Alternatively, these findings
may suggest a lack of impact of estrogen and progesterone levels on
recurrence in low-grade endometrial stromal sarcoma. On the other
hand, based on limited evidence, hormonal replacement therapy with
or withour progesterone may be associated with a higher relapse rate
and is not recommended.52
A major strength of our study is the fact that we were able to pool
data from a large number of patients with low-grade endometrial
stromal sarcoma providing enough statistical power to draw conclu-
sions. However, certain limitations should be noted. First, we could not
fully control for clinicopathological characteristics such as stage and
tumor size and for the administration of any adjuvant therapy. Also,
due to the lack of central pathology review, we could not exclude the
Nasioudis D, et al. Int J Gynecol Cancer 2019;29:126–132. doi:10.1136/ijgc-2018-000063
Original Article
Int J Gynecol Cancer: first published as 10.1136/ijgc-2018-000063 on 7 January 2019. Downloaded from http://ijgc.bmj.com/ on 2 April 2019 by guest. Protected by copyright.
inadvertent inclusion of non-low-grade endometrial stromal sarcoma
cases, especially given the recent reclassification of endometrial
sarcomas. However, the majority of the alterations in the 2014 World
Health Organization classification system are most relevant to high-
grade endometrial stromal sarcoma and undifferentiated endometrial
stromal sarcoma. Our investigation is limited to low-grade endometrial
stromal sarcoma (<10 mitoses). It should be noted that mitotic figures
are no longer required to discriminate low-grade from high-grade
endometrial stromal sarcoma since the mutation (YWHAE-FAM22)
is more useful. Moreover, while all included studies provided data on
tumor relapse, subsequent subset analyses included a fraction of the
total patient population. Lastly, due to the extremely low incidence of
low-grade endometrial stromal sarcoma, the performance of prospec-
tive randomized trials is not feasible. All studies included in the present
meta-analysis were retrospective so of low quality.
In conclusion, ovarian preservation for women with low-grade
endometrial stromal sarcoma is associated with an increased risk of
tumor relapse but, based on limited evidence, not with an increased
risk of death. Based on the results of our study, ovarian preservation
cannot be routinely recommended. However, it could potentially be
considered in carefully selected young pre-menopausal women with
disease confined to the uterus following extensive counseling. Unfor-
tunately, there are no prospective randomized investigations to guide
recommendations. Given the limited data, providers should review
available studies, national and international guidelines with pre-meno-
pausal patients with low-grade endometrial stromal sarcoma. After an
informed discussion, an individualized plan should be made with each
patient. Due to the rarity of this tumor, the creation of an international
uterine sarcoma registry could aid in elucidating the optimal manage-
ment of these patients.
Funding  The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not-for-profit sectors.
Competing interests  None declared.
Provenance and peer review  Not commissioned, externally peer reviewed.
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