Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 532e536

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Taiwanese Journal of Obstetrics & Gynecology

journal homepage: www.tjog-online.com

Original Article

Outcome of ovarian preservation during surgical treatment for

endometrial cancer: A Taiwanese Gynecologic Oncology Group study
Hei-Yu Lau a, b, Min-Yu Chen c, Yu-Min Ke d, Jen-Ruei Chen e, n, I-Hui Chen f,
Wen-Shiung Liou g, Hung-Chun Fu h, Cheng-Chang Chang i, Keng-Fu Hsu j,
Kung-Liahng Wang k, l, m, *
a
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan
b
Department of Obstetrics and Gynecology, National Yang-Ming University, Taipei, Taiwan
c
Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan
d
Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, Taiwan
e
Division of Gynecology Oncology, Mackay Memorial Hospital, Taipei, Taiwan
f
Department of Obstetrics and Gynecology, National Taiwan University Hospital, Tsin-Chu Branch, Tsinchu, Taiwan
g
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
h
Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
i
Department of Obstetrics and Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
j
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
k
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, and Mackay Medical College, Taipei, Taiwan
l
Department of Nursing, Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
m
Department of Obstetrics and Gynecology, Taipei Medical University, Taipei, Taiwan
n
Mackay Medicine, Nursing and Management College, Taipei, Taiwan

a r t i c l e i n f o a b s t r a c t

Article history: Objective: The goal of this study was to investigate the impact of ovarian preservation on the survival of
Accepted 22 October 2014 women with early-stage endometrial cancer, particularly young women.
Materials and methods: A study cohort of 64 patients with histologically conrmed early-stage endo-
Keywords: metrial cancer was retrospectively collected from 10 member hospitals of the Taiwanese Gynecologic
early-stage cancer Oncology Group between 1998 and 2009. Survivorship and overall survival were compared between
endometrial cancer
these two groups using a log-rank test.
ovarian preservation
Results: All patients who underwent surgery were adult women with a mean age of 40.4 9.2 years
(range 24e63 years). Ovary-preserving surgery was performed in 38 (59.4%) patients who desired to
preserve their ovaries, incidentally in 19 (29.7%) patients with a preoperative diagnosis other than
endometrial carcinoma, and in seven patients (10.9%) with unknown reasons. The 5-year recurrence-free
survival rate was 98.3% with a median follow up of 44.6 months (range 1.0e126.9 months). Eight patients
required adjuvant treatment (12.5%); one patient had documented local recurrence (1.6%); and no
metachronous ovarian malignancy occurred during follow up.
Conclusion: Preservation of bilateral ovaries does not increase cancer-related mortality. A more conser-
vative approach to surgical staging may be considered in premenopausal women with early-stage
endometrial cancer without risk factors.
Copyright 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All
rights reserved.

Introduction

Uterine cancer remains one of the leading causes of cancer

mortality in women worldwide. Approximately 287,100 women
* Corresponding author. 1, Lane 303, Changsha Street, Mackay Memorial Hospital, developed uterine cancer with a mortality rate of 1.7 to 2.4 per
Taitung, Taiwan. 100,000 women in 2008 worldwide [1]. In Taiwan, the incidence
E-mail address: KL421229@ms6.hinet.net (K.-L. Wang).

http://dx.doi.org/10.1016/j.tjog.2014.10.010
1028-4559/Copyright 2015, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
 H.-Y. Lau et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 532e536 533

rate increased from 6.17 to 10.86 per 100,000 from 2001 to 2011 [2]. examination. The research was approved by the respective Insti-
The primary treatment for early-stage endometrial cancer involves tutional Review Boards and Ethics Committees of the 10 member
hysterectomy and bilateral salpingo-oophorectomy (BSO) [3]. The hospitals of the TGOG.
BSO procedure aims to exclude occult ovarian metastases and Frequency was presented for categorical variables. Survival
decrease estrogen production; given that endometrial cancer is an analysis was evaluated using KaplaneMeier test, and statistical
estrogen-responsive disease. However, ever since the 1988 Inter- differences in survival were compared using a log-rank test. All
national Federation of Gynecology and Obstetrics (FIGO) guidelines reported p values corresponded to two-sided tests, and a p
for endometrial cancer staging [4], there has been controversy value < 0.05 was considered signicant. All analyses were carried
regarding the necessity of aggressive surgical staging, including out using SPSS version 17 software (SPSS, Chicago, IL, USA).
BSO and lymphadenectomy, particularly in young women with
early-stage disease. Traditionally, endometrial cancer has been
Results
considered a disease of postmenopausal women with a median age
of 52e54 years [2]. However, a recent study has shown that up to
The clinicopathological proles and treatment modalities of the
14% of women with endometrial cancer are premenopausal [5]. In
study cohort are listed in Table 1. More than three-fths of the
Taiwan, > 30% of cases occur in premenopausal patients and 10% in
patients (67.2%) were young women < 45 years of age (mean
women under the age of 40 years [2]. The immediate consequence
40.4 9.2 years, range 24e63 years) at initial diagnosis. FIGO stages
of the BSO procedure leads to surgical menopause in young women,
IA and IB were the most common postoperative surgical stages,
leading to undesired climacteric symptoms, particularly hot
which represented approximately four-fths of all patients (53/64,
ushes, sleep disorders, and long-term effects, as well as long-term
83%). The most frequent preoperative diagnosis associated with
risks to cardiovascular and bone health [3]. Nevertheless, the BSO
hysterectomy was endometrial carcinoma (46.9%), followed by
procedure may not be necessary in women with early-stage
endometrial carcinoma due to the relatively low incidence of
ovarian metastases. Only ~5% of these women have ovarian me- Table 1
tastases [6,7]. The prognosis for endometrial carcinoma in pre- Patient characteristics.
menopausal women tends to be favorable, with a 5-year survival Characteristics Patients with
rate > 90% in early-stage disease [8]. Ali-Fehmi et al [9] suggested retained ovaries
that early-stage, well-differentiated endometrial cancer is most (n 64)
commonly encountered in young patients. Moreover, Lee et al [10] n %
reported that the risk of a coexisting malignancy is negligible in Age, y
patients with minimal preoperative risk factors and no intra- 30 10 15.6
operative evidence of advanced disease. Since no prospective 31e35 11 17.2
clinical trial is currently available on the survival outcomes of BSO 36e40 13 20.3
41e45 9 14.1
versus ovarian conservation at hysterectomy, the present study
>45 21 32.8
aimed to investigate the impact of ovarian preservation on the Type of hysterectomy
survival of women with early-stage endometrial cancer, particu- TAH 35 54.7
larly in young women. LAVH 24 37.5
TVH 3 4.7
RH/MRH 2 3.1
Materials and methods Preoperative diagnosis
Endometrial carcinoma 30 46.9
Individual patient data of histologically conrmed, early-stage Endometrial hyperplasia 22 34.4
endometrial cancer (Types I and II) were retrospectively collected Leiomyoma/adenomyosis 9 14.1
Uterine prolapse 3 4.6
from the data registry of the 10 member hospitals of the Taiwanese
Reasons for ovarian preservation
Gynecologic Oncology Group (TGOG) between 1998 and 2009. A Young age (45 y) and/or patient's desire 38 59.4
total of 6098 patients were initially identied from the registries
during the study period, among whom, 72 patients had either Other preoperative diagnosisa 19 29.7
unilateral or bilateral ovarian preservation. After excluding patients Unknown 7 10.9
Myometrial invasion
with unilateral ovarian preservation, 64 patients were included in <1/2 58 90.6
the nal analysis. Detailed information on the patients was care- 1/2 6 9.4
fully reviewed and extracted from individual medical charts. Pa- Final histology
rameters abstracted from the medical documents included age at Endometrioid 55 85.9
Nonendometrioid 9 14.1
diagnosis, gravity and parity, preoperative diagnosis, date of diag-
Histological grade
nosis, reasons for preserving ovaries, date of recurrence, date of last 1 51 79.7
follow up, follow-up results for recurrence or secondary malig- 2 12 18.8
nancies, histological type, stage, grade, tumor size, lymphovascular 3 1 1.5
space involvement, lymph node metastases, depth of myometrial Postoperative FIGO stage (incompleteb)
Ia 38 59.4
invasion, and disease-free and overall survival. Evidence of recur- Ib 15 23.4
rence was conrmed by pathological or radiological examination. Ic 4 6.3
The follow-up time was dened as the time from initial diagnosis to IIa 6 9.4
the time of death or last follow up. Disease-free survival was IIb 1 1.5
calculated as the number of months from cancer diagnosis to date a
Diagnosis that does not require oophorectomy and incidental ovarian
of recurrence or last follow up. Tumor staging was assigned in preservation.
b
accordance with the FIGO 1988 staging system. Stage of tumor was Unevaluated areas, such as both adnexae, or lymph node status were considered
negative. FIGO International Federation of Gynecology and Obstetrics;
assigned based on available pathological ndings, and unevaluated LAVH laparoscopy assisted vaginal hysterectomy; MRH modied radical hys-
areas such as both adnexa and lymph node status were considered terectomy; RH radical hysterectomy; TAH total abdominal hysterectomy;
negative for metastatic disease based on intraoperative TVH total vaginal hysterectomy.
534 H.-Y. Lau et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 532e536

endometrial hyperplasia (34.4%), benign leiomyoma or adeno- early-stage endometrial cancer. Although we do not know if the
myosis (14.1%), and uterine prolapse (4.6%). Only ve patients un- recurrence was associated with hormonal inuences due to a re-
derwent either total vaginal hysterectomy or (modied) radical sidual ovary or occult metastasis, the sites of recurrence offered no
hysterectomy, whereas the remaining 59 patients underwent total evidence to support the suspicion that residual ovaries had inu-
abdominal hysterectomy or laparoscopy-assisted vaginal hyster- enced disease recurrence. A search of the literature revealed that
ectomy. Histological diagnosis of pelvic lymph nodes was available women who underwent bilateral oophorectomy before the age of
in 14 of the 64 patients, and all were negative for metastasis. Eight 45 years may be associated with an increased risk of 67% in all-
patients with high-risk factors had adjuvant treatments without cause mortality [11]. To avoid the short- and long-term conse-
additional bilateral adnexectomy: two with chemotherapy (2/8, quences of surgical menopause, there is a strong rationale for
25%) and six with pelvic radiotherapy (6/8, 75%). Ovarian preser- ovarian preservation in young women. We must consider two
vation was performed predominately among young patients (45 questions before we can answer whether saving perfectly normal
years old), with or without patients' request among those with and functional ovaries without predictable risk factors is acceptable
preoperative diagnosis of endometrial cancer, followed by women in patients with early-stage endometrial cancer. First, we must
who were preoperatively diagnosed with benign disease and consider the risk of leaving occult ovarian metastasis or a coexisting
without gross ndings of adnexa (e.g., endometrial hyperplasia, synchronous primary tumor within the ovary. Second, we must
leiomyoma, or adenomyosis). The reasons for ovarian preservation consider the activation of microscopic foci of residual endometrial
were not obvious based on the medical record review of seven cancer by endogenous estrogen.
patients. Most would agree that the risk of leaving occult ovarian
The 5-year recurrence-free survival rate was 98.3% with a me- metastasis or a coexisting synchronous primary tumor within the
dian follow up of 44.6 months (range 1.0e126.9 months; Figure 1). ovary is of primary concern. Although the incidence of coexisting
There was no signicant difference in disease-free survival be- ovarian tumors has been shown to range from 5% to 29% [12e16],
tween patients who desired ovarian preservation versus others these reports failed to mention whether these patients had extra-
with incidental ovarian preservation (log-rank test, p 0.270). uterine diseases. Lee et al [10] reviewed 260 patients with a mean
Overall, one patient had documented local vaginal stump recur- age of 51.8 years. These authors identied a nonendometrioid
rence (1.6%), and another Stage I patient with endometrioid his- histological subtype, intraoperative extrauterine disease, lymph
tology had recurrence. No metachronous ovarian malignancy was node metastases, and age as independent risk factors for adnexal
observed during follow up. metastases in women with early stage and grade of endometrial
carcinoma [10]. They found a 7.3% coexisting malignancy rate, but
Discussion this was only 0.97% in patients without any evidence of intra-
operative gross extrauterine disease. Another study reviewed 178
We found a relatively low recurrence rate (1.6%) in the preser- cases of surgically treated patients with or without BSO, and they
vation of bilateral ovaries at hysterectomy among patients with suggested that ovarian preservation does not affect disease

Figure 1. Disease-free survival in patients with ovarian preservation.

 H.-Y. Lau et al. / Taiwanese Journal of Obstetrics & Gynecology 54 (2015) 532e536 535

Table 2
Characteristics of review literature.

Authors

Wright et al [5] Richter et al [24] Sun et al [25] Lee et al [26] Present study

Patient, n (ovarian preservation) 402 20 34 176 64

Age (y)  45  45  45  45 40.4 9.2
Stage IaeIc IaeIc IaeIc IeII IeII
Ia (%) 64 71 90.3 59.4
Ib (%) 33 22 23.4
Ic (%) 3 7 3.4 6.3
II (%) 6.3 10.9
Grade
I (%) 79 70 75.6 79.7
II (%) 14 20 22.7 18.8
III (%) 3 10 107 1.5
Histologic type
Endometrioid (%) 100 87 97 100 85.9
Non-endometrioid (%) 13 3 14.1
5-year survival (%) 98 100 93.2 94.3 98.3
Recurrence (%) 5.0 2.3 1.6

recurrence or overall survival in clinical Stage I and II endometrial sensitivity of small occult lesions and its false positivity due to
cancer [17]. In our study, metachronous ovarian malignancy was physiological uptake [22,23].
not observed during follow up. The current study nds that the ovarian preservation is a
Many would suggest that the activation of microscopic foci of possible alternative in patients with early-stage endometrial can-
residual endometrial cancer by endogenous estrogen is of clinical cer, and does not increase cancer-related mortality. A more con-
signicance. However, this theoretical relation lacks not only servative approach to surgical staging may be considered in
large-scale epidemiological association, but also clinical evidence. premenopausal women with early-stage endometrioid endome-
Barakat et al [18] reported a prospective trial of estrogen trial cancer. However, the performance of ovarian preservation is
replacement therapy in >1200 women with endometrial cancer highly individualized; patients who desire ovarian preservation
conducted by the Gynecologic Oncology Group. Although the should receive a full explanation of the potential risks from their
study ended early, the absolute recurrence rate was only 2.1% physicians; and genetic tests may be necessary in patients with a
[hazard ratio (HR) 1.27, 95% condence interval (CI) 0.92e1.77]. family history of related malignancies. We suggest that the pres-
Another large cohort study analyzed 3269 women; ovarian pres- ervation of bilateral ovaries is not suitable for endometrial cancer
ervation had no effect on either cancer-specic survival (HR 0.58, patients with extrauterine spread at preoperative and intra-
95% CI 0.14e2.44) or overall survival (HR 0.68, 95% CI 0.34e1.35). operative assessment. These patients should also have longer than
The ndings suggested that ovarian preservation in premeno- typical follow up than those who have a BSO procedure at hyster-
pausal women with early-stage, low-grade endometrial cancer ectomy, and careful intraoperative assessment of the adnexa is also
might be safe and not associated with an increased risk of cancer- mandatory. Nevertheless, the current study is the only study to
related mortality [5]. In our study, favorable survival (98.3%) was report the experiences with the follow-up results of patients that
also found in patients with ovarian preservation. Comparing the have undergone ovary-preserving surgery.
subgroup of ovarian preservation with prediagnosis known and
unknown endometrial cancer, a favorable prognosis was likely Conicts of interest
noted in patients with unknown cancer, even if it was not statis-
tically signicant. Therefore, for patients approaching early-stage The authors declare no conicts of interest.
malignancy incidentally diagnosed on hysterectomy, these
women may not need additional procedures if BSO is not per- Acknowledgments
formed at the time of initial hysterectomy. Similar to prior studies,
there was no signicant difference in survival in our study This study was supported by a grant from the Taiwanese Gy-
(Table 2), which reveals the feasibility and safety of ovarian pres- necological Oncology Group (MOST 103-2325-B-195-002-). The
ervation in patients with early-stage, low-grade endometrial authors would like to thank member hospitals of the Taiwanese
cancer. Gynecologic Oncology Group (TGOG) and their staffs for helpful
The current study was limited by the inherent nature of a comments, discussions, and support during data collection.
hospital-based, retrospective study, and this must be borne in
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