Borderline ovarian tumors: clinical characteristics, management, and outcomes - a multicenter study

Abstract

Background
The optimal surgical management and staging of borderline ovarian tumors (BOTs) are controversial. Institutions have different surgical approaches for the treatment of BOTs. Here, we performed a retrospective review of clinical characteristics, surgical management and surgical outcomes, and sought to identify variables affecting disease-free survival (DFS) and overall survival (OS) in patients with BOTs. MethodsA retrospective review of ten gynecological oncology department databases in Turkey was conducted to identify patients diagnosed with BOTs. The effects of type of surgery, age, stage, surgical staging, complete versus incomplete staging, and adjuvant chemotherapy were examined on DFS and OS. ResultsIn total, 733 patients with BOTs were included in the analysis. Most of the staged cases were in stage IA (70.4 %). In total, 345 patients underwent conservative surgeries. Recurrence rates were similar between the conservative and radical surgery groups (10.5 % vs. 8.7 %). Furthermore we did not find any difference between DFS (HR = 0.96; 95 % confidence interval, CI = 0.7–1.2; p = 0.576) or OS (HR = 0.9; 95 % CI = 0.8–1.1; p = 0.328) between patients who underwent conservative versus radical surgeries. There was also no difference in DFS (HR = 0.74; 95 % CI = 0.8–1.1; p = 0.080) or OS (HR = 0.8; 95 % CI = 0.7–1.0; p = 0.091) between complete, incomplete, and unstaged patients. Furthermore, receiving adjuvant chemotherapy (CT) for tumor stage ≥ IC was not an independent prognostic factor for DFS or OS. Conclusions
Patients undergoing conservative surgery did not show higher recurrence rates; furthermore, survival time was not shortened. Detailed surgical staging, including lymph node sampling or dissection, appendectomy, and hysterectomy, were not beneficial in the surgical management oF BOTs.

Full text

R E S E A R C H Open Access
Borderline ovarian tumors: clinical
characteristics, management, and
outcomes - a multicenter study
Mehmet Gokcu
1
, Kemal Gungorduk
2*
, Osman Aşıcıoğlu
3
, Nilüfer Çetinkaya
4
, Tayfun Güngör
4
, Gonca Pakay
5
,
Zeliha Fırat Cüylan
4
, Tayfun Toptaş
6
, Ramazan Özyurt
7
, Elif Ağaçayak
8
, Aykut Ozdemir
9
, Onur Erol
10
,Anıl Turan
11
,
Varol Gülseren
1
, Mehmet Sait İcen
8
, Taylan Şenol
5
, Hakan Güraslan
9
, Burcu Yücesoy
8
, Ahmet Sahbaz
11
,
Ozgu Gungorduk
1
, Berhan Besimoğlu
3
, Kaan Pakay
5
, Osman Temizkan
3
, Muzaffer Sancı
1
, Tayup Şimşek
6
,
Mehmet Mutlu Meydanlı
4
, Mehmet Harma
11
, Levent Yaşar
9
, Birtan Boran
7
, Aysel Derbent Uysal
10
and AteşKarateke
5
Abstract
Background: The optimal surgical management and staging of borderline ovarian tumors (BOTs) are controversial.
Institutions have different surgical approaches for the treatment of BOTs. Here, we performed a retrospective review
of clinical characteristics, surgical management and surgical outcomes, and sought to identify variables affecting
disease-free survival (DFS) and overall survival (OS) in patients with BOTs.
Methods: A retrospective review of ten gynecological oncology department databases in Turkey was conducted to
identify patients diagnosed with BOTs. The effects of type of surgery, age, stage, surgical staging, complete versus
incomplete staging, and adjuvant chemotherapy were examined on DFS and OS.
Results: In total, 733 patients with BOTs were included in the analysis. Most of the staged cases were in stage
IA (70.4 %). In total, 345 patients underwent conservative surgeries. Recurrence rates were similar between the
conservative and radical surgery groups (10.5 % vs. 8.7 %). Furthermore we did not find any difference between
DFS (HR = 0.96; 95 % confidence interval, CI = 0.7–1.2; p=0.576)orOS(HR=0.9;95%CI=0.8–1.1; p= 0.328) between
patients who underwent conservative versus radical surgeries. There was also no difference in DFS (HR = 0.74; 95 %
CI = 0.8–1.1; p=0.080)orOS(HR=0.8;95%CI=0.7–1.0; p= 0.091) between complete, incomplete, and unstaged
patients. Furthermore, receiving adjuvant chemotherapy (CT) for tumor stage ≥IC was not an independent prognostic
factor for DFS or OS.
Conclusions: Patients undergoing conservative surgery did not show higher recurrence rates; furthermore, survival
time was not shortened. Detailed surgical staging, including lymph node sampling or dissection, appendectomy, and
hysterectomy, were not beneficial in the surgical management oF BOTs.
Keywords: Borderline ovarian tumor, Adjuvant chemotherapy, Surgery
* Correspondence: maidenkemal@yahoo.com
2
Department of Gynecology and Gynecologic Oncology, Mugla SıtkıKocman
University Education and Research Hospital, Mentese 48000, Mugla, Turkey
Full list of author information is available at the end of the article
© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Gokcu et al. Journal of Ovarian Research (2016) 9:66
DOI 10.1186/s13048-016-0276-1
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Background
Taylor first described a type of ovarian tumor in 1929 that
was different from both benign and malignant epithelial
ovarian tumors [1]. Then, in 1973, the World Health
Organization (WHO) assigned the name ‘borderline’to
these tumors, with morphological criteria (especially the
absence of stromal invasion) [2]. Borderline ovarian
tumors (BOTs) are currently staged according to the
International Federation of Gynecology and Obstetrics
(FIGO) classification of ovarian cancer; they represent
~10–20 % of all ovarian neoplasias [3]. They are diag-
nosed in younger women, at an earlier stage, and have
a better prognosis than malignant ovarian tumors [4].
The 5-year survival rates are 95–97 % and ~70 % of
thesetumorsarestageIatthetimeofdiagnosis[3].
Preoperative diagnosis of BOTs remains difficult [5].
Cancer antigen 125 (CA-125) is the most helpful avail-
able marker in the diagnosis of advanced-stage cases [6].
Moreover, the optimal surgical management and staging
of BOTs are controversial. Institutions have different
surgical approaches for the treatment of BOTs. Some
surgeons prefer comprehensive surgical staging, including
lymphatic sampling or dissection, while others exclude the
lymph nodes [4, 7].
The purposes of the present study were to perform a
retrospective review of the clinical characteristics, surgi-
cal management, and surgical outcomes, and to identify
variables affecting survival in 733 patients with BOTs who
were treated at ten gynecology departments in Turkey.
We also sought to explore the following issues:
1) Is surgical staging (including lymphadenectomy)
necessary in all patients?
2) Is appendectomy necessary in patients with
mucinous BOTs?
3) Which type of procedure should the surgeon choose
in patients with BOTs (radical vs. conservative)?
4) Should patients with BOTs receive adjuvant
chemotherapy after the surgery if they have a tumor
stage ≥IC, as with epithelial ovarian tumors?
5) What is the function of analyzing frozen sections
during BOT surgery? Do the results differ between
serous and mucinous types?
6) What should the surgeon do in patients with
recurrent BOTs?
7) What are the prognostic factors for overall and
disease-free survival in patients with BOTs?
Methods
This retrospective study was performed using 10
gynecological oncology department databases (Izmir
Tepecik Education and Research Hospital, Antalya
Akdeniz University School of Medicine, Dicle University
School of Medicine, Zekai Tahir Burak Education and
Research Hospital, Zonguldak Bulent Ecevit University
School of Medicine, Antalya Education and Research
Hospital, Zeynep Kamil Education and Research Hospital,
Istanbul Bakırköy Sadi Konuk Education and Research
Hospital, Sisli Hamidiye Etfal Education and Research
Hospital, and Istanbul Education and Research Hospital).
All patients with BOTs diagnosed between January 1, 1998
and December 31, 2014 were included.
This study was approved by the ethics committee. It
was conducted in accordance with the ethical standards
of the Declaration of Helsinki.
From the hospital databases, patient age, menopausal
state, pre-operative CA-125, and preoperative ultrasound
images were collected. Furthermore, the surgical tech-
nique, histological type, mean tumor diameter, lymph node
status, stage at diagnosis, final pathological diagnosis, and
accompanying pathologies, if any, were reviewed. Addi-
tionally, chemotherapy after surgery, postoperative follow-
up periods, and data related to disease recurrence were
evaluated. If frozen sections (FS) were analyzed intraopera-
tively, FS results were reported intraoperatively as benign,
borderline tumor, at least borderline tumor, or malignant
tumor. Patients with incomplete data were excluded from
the analysis.
The International Federation of Gynecology and Obstet-
rics (FIGO) 2009 staging scheme for epithelial ovarian
carcinomas was used in all patients [8]. Although the FIGO
ovarian staging classification was revised on January 1,
2014, we used the previous staging classification for 2014
patients for consistency. Surgical procedures were classified
as radical or conservative. If both ovaries were removed,
this was included in the radical group. The conservative
group included fertility sparing surgeries (such as unilateral
salpingo-oophorectomy (USO), cystectomy, bilateral
cystectomy, cystectomy with contralateral ovarian biopsy,
and bilateral ovarian biopsies) in women who were pre-
menopausal or wished to preserve their fertility. Moreover,
patient operations were categorized into three groups:
complete staging, incomplete staging, or unstaged proce-
dures. Complete staging was defined as peritoneal washing
and/or biopsies, pelvic and paraaortic lymphadenectomy
(sampling or complete), and omentectomy being per-
formed. If only peritoneal washing and omental and/or
peritoneal biopsies without lymphadenectomy were per-
formed, this was considered incomplete staging. Further-
more, if only ovarian surgery (only ovarian cystectomy
or oopherectomy) was performed, this was considered
unstaged. Additionally, if the patients underwent only
an appendectomy with ovarian surgery, they were clas-
sified in the unstaged group.
Survival analysis was based on the Kaplan-Meier method
and results were compared using the log-rank test.
Disease-free survival (DFS) was defined as the time
from the date of primary surgery to the detection of
Gokcu et al. Journal of Ovarian Research (2016) 9:66 Page 2 of 8
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recurrence or the latest observation. Overall survival
(OS) was defined as the time from the date of primary
surgery to death or the latest observation. The χ
2
test
and Student’s t-test for unpaired data were used for
statistical analyses. Cox regression analysis was used to
determine factors affecting survival, and results are pre-
sented as hazard ratios (HR). All statistical analyses
were performed using the Med-Calc software (ver. 11.5
for Windows; MedCalc Software, Mariakerke, Belgium).
Apvalue < 0.05 was considered to indicate statistical
significance.
Results
We evaluated 733 patients with BOTs during the study
period. The characteristics of the patients are shown in
Table 1. There was recurrence in 69 (9.4 %) of the
patients: 35 (50.7 %) in the conservative surgery group
and 34 (49.3 %) in the radical surgery group (the difference
was not statistically significant, p=0.405) (Table 2).
Furthermore no statistically significant difference in re-
currence was observed between complete, incomplete,
and unstaged patients (9.6, 12.3, and 8.4 %, respectively;
p= 0.615). Most of the recurrent patients were treated
with surgery; 10 were managed with chemotherapy, 47
were managed with surgery, and 12 were managed with
chemotherapy after surgery. During the follow-up period,
in total, 10 (1.4 %) patients died from their disease.
In 407 patients, frozen section analyses were carried
out. Benign, borderline, at least borderline, and malig-
nancies were seen in 30 (7.3 %), 251 (61.6 %), 117
(16.0 %), and 9 (2.2 %) patients, respectively. The accur-
acy of frozen section analyses in serous type tumors was
significantly higher than in the mucinous type (94 % vs.
80 %; p< 0.001).
In total, 101 patients received adjuvant chemotherapy
(CT). During the study period, postoperative CT was ad-
ministered for FIGO stage IC and more advanced stages
or recurrent disease. Of the 101 patients, 25 received
CT for recurrent disease, 36 for early stage disease
(stage IC or II, 36/76 patients), and 40 received CT for
advanced-stage disease (stage III or IV, 40/76 patients).
Postoperative CT regimens consisted of cisplatin +
paclitaxel (37/101 patients), carboplatin + paclitaxel
(55/101 patients), cisplatin + doxorubicin + cyclophos-
phamide (4/101 patients), cisplatin + cyclophosphamide
(3/101 patients), and cisplatin + amifostin (2/101 patients)
for 3–6cycles.
Surgical characteristics of the patients are shown in
Table 2. In total, 388 (52.9 %) patients underwent radical
excision procedures, while 345 (47.1 %) underwent con-
servative surgical procedures. An appendectomy was
performed in 289 (38.4 %) cases. The number of patients
with appendicial involvement was 23 (3.1 %); 21 of them
were in the mucinous group (2.8 %).
We next analyzed the patients by dividing them into
two groups according to the median age (<40 vs. ≥40).
All parameters were similar between the groups (Table 3).
TheresultsofthemultivariateanalysesofDFSandOS
are shown in Table 4. In the multivariate analysis, per-
formance of surgical staging (or not), FIGO stage, age
(<40 or ≥40), menopausal status, presence of an inva-
sive implant, performance of radical surgery, lymphade-
nectomy, and adjuvant CT for tumor stage ≥IC were
not independent prognostic factors for DFS or OS
(Table 4).
With a Kaplan-Meier analysis, we did not find any dif-
ference in DFS (HR = 0.96; 95 % CI = 0.7–1.2; p= 0.576)
or OS (HR = 0.9; 95 % CI = 0.8–1.1; p= 0.328) between
patients who underwent conservative versus radical sur-
geries. There was also no difference in DFS (HR = 0.74;
95 % CI = 0.8–1.1; p= 0.080) or OS (HR = 0.8; 95 %
Table 1 Demographic characteristics of patients with borderline
ovarian tumors
Age
Median (n, range in years) 41.2 (16–82)
< 40 years (n, %) 353 (48.2)
≥40 years (n, %) 380 (51.8)
Postmenopausal status (n, %) 227 (31.0)
Histology
Serous (n, %) 534 (72.9)
Mucinous (n, %) 160 (21.8)
Other (n, %) 39 (5.3)
Ultrasound image
Solid (n, %) 110 (15.0)
Cystic (n, %) 130 (17.7)
Unknown (n, %) 493 (67.3)
Median CA-125 level (U/mL) 89 (1–3394)
Median size (mm) 112.02 ± 64.57
Stage in diagnosis (n,%)
IA 516 (70.4)
IB 74 (10.1)
IC 64 (8.7)
IIA 2 (0.3)
IIB 6 (0.8)
IIC 8 (1.1)
IIIA 0
IIIB 11 (1.5)
IIIC 52 (7.1)
IV 0
Disease-free survival (n, range in months) 51.7 (1–216)
Overall survival (n, range in months) 55.2 (1–216)
Duration of follow-up (n, range in months) 55.2 (1–216)
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CI = 0.7–1.0; p= 0.091) between complete, incomplete,
and unstaged patients. When the impact of lymph
node sampling or dissection on DFS and OS was
assessed, lymph node removal had no effect on DFS
(HR = 1.2; 95 % CI = 0.9–1.4; p=0.465) or OS (HR=1.1;
95 % CI = 1.0–1.3; p= 0.623). Furthermore, there was no
difference in DFS (HR = 1.3; 95 % CI = 1.1–1.5; p=0.410)
or OS (HR = 0.8; 95 % CI = 0.6–1.1; p=0.856) between
patients treated with surgery alone, chemotherapy alone,
or sequential treatment for recurrent BOT. Similarly, in
patients who underwent cystectomies or oopherectomies,
there was no difference in DFS (HR = 0.8; 95 % CI =
0.7–1.1; p=0,132) or OS (HR=0.7; 95 % CI=0.6–0.8;
p= 0.212). In BOTs, adding an appendectomy to the
surgical procedure had no effect on DFS (HR = 0.9;
95 % CI = 0.7–1.1; p= 0.270) or OS (HR = 1.0; 95 %
CI = 0.7–1.3; p= 0.320). In patients who underwent
hysterectomies (vs. not), there was no also no differ-
ence in DFS (HR = 1.1; 95 % CI = 0.9–1.2; p= 0.208)
or OS (HR = 1.4; 95 % CI = 1.1–1.7; p= 0,416). Finally,
performing (vs. not) an appendectomy in mucinous
BOT patients had no effect on DFS (HR = 0.9; 95 %
CI = 0.7–1.3; p= 0.990) or OS (HR = 0.8; 95 % CI =
0.6–0.9; p= 0.751).
We also analyzed the patients by dividing them into
two groups according to recurrence (vs. not). All pa-
rameters were similar between groups (Table 5). The
results of univariate and multivariate analyses for recur-
rence are shown in Table 5. In univariate and multivariate
analyses, age (<40 vs. ≥40), FIGO stage (≥IC vs. < IC),
performance of radical surgery, and performance of surgi-
cal staging (vs. not) were not independent risk factors for
the recurrence of BOTs (Table 6).
Discussion
In this study, we performed a retrospective analysis of
733 patients with BOTs who were treated with surgery
at 10 gynecology centers in Turkey. BOTs are classified
as a separate entity within ovarian malignancies because
of their atypical properties. Furthermore, they are not a
rare clinical entity, constituting ~10–20 % of all ovarian
neoplasias in clinical studies [3]. The present study is
one of the largest reported series of cases with BOTs.
Table 2 Pathological and surgical characteristics of patients
with borderline ovarian tumors
Frozen pathology records (n,%)
Benign 30 (7.3)
Borderline 251 (61.6)
At least borderline 117 (28.7)
Malignant 9 (2.2)
Accuracy of frozen pathology (n, %)*
Serous (n, %) 288 (94)
Mucinous (n, %) 67 (80)
Surgery Type (n,%)
Conservative 345 (47.1)
Radical 388 (52.9)
Conservative surgery type (n,%)
Unilateral cystectomy 106 (30.7)
Bilateral cystectomy 20 (5.7)
Cystectomy and contralateral ovarian biopsy 7 (2.0)
Unilateral salpingo-oopherectomy (USO) 194 (56.2)
USO and contralateral ovarian biopsy 17 (4.9)
Bilateral ovarian biopsy 1 (0.2)
Staging surgery (n,%)
None 273 (37.2)
Yes
Complete 395 (53.9)
Incomplete 65 (8.9)
Received postoperative chemotherapy 101 (13.8)
Appendectomy (n, %) 289 (39.4)
Appendectomy with serous histology 159
Appendectomy with mucinous histology 130
Appendicial involvement (n, %) 23 (3.1)
Appendicial involvement + mucinous type 21 (2.8)
Hysterectomy (n, %) 436 (59.5)
Median removed lymph nodes
(n, range in numbers)
25.7 ± 22.2 (2–173)
Surgery type (n,%)
Laparascopy 34 (4.6)
Laparotomy 699 (95.4)
Recurrence (n, %) 69 (9.4)
Treatment after recurrence**
Surgery 47 (6.4)
Chemotherapy 10 (1.4)
Surgery + Chemotherapy 12 (1.6)
Recurrence (n, %)***
Conservative group 35 (10.5)
Radical group 34 (8.7)
Table 2 Pathological and surgical characteristics of patients
with borderline ovarian tumors (Continued)
Recurrence (n, %)****
Unstaging 23 (8.4)***
Incomplete staging 8 (12.3)
Complete staging 38 (9.6)
*P< 0.001
**P< 0.001
***P= 0.405
****P= 0.615
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Similar to previous studies, the mean age of patients
with BOTs was 41.2 years in our study. Of the 733 pa-
tients with the tumor, 353 (48.1 %) were < 40 years old;
our result adds to current knowledge on the occurrence
of BOTs in younger and premenopausal women [9–11].
Furthermore, we found that clinical features were similar
between the groups aged under and over 40 years. Con-
sistent with previous studies [11, 12], the most common
histological type was a serous BOT in the present
study. However, the rate of serous histology (72.9 %)
was significantly higher than in several previous studies
[13, 14]. Heterogeneity of the mucinous tumors may be
areasonforthis.
The most commonly discussed questions about BOTs
are as follows. We address each in turn.
1) Is surgical staging (including lymphadenectomy)
necessary in all patients?
In our study, more than half of our patients were
staged surgically, and most of them were staged
completely, similar to the ovarian cancer surgery
situation. However, we found no difference between
the survival rates of staged and unstaged patients.
Furthermore, no difference was found between
completely and incompletely staged patients.
These results were similar to previous studies
[13–15]. We found that lymph node removal in
surgical staging did not affect survival, as in
Güvenal et al.’s study [13]. Similarly, Fauvet et al.
suggested that lymph node removal is not a part
of surgical staging for BOTs [7].
2) Is appendectomy necessary in patients with
mucinous BOTs?
Adding an appendectomy to surgical staging
procedures has been recommended for mucinous
tumors, in particular [4]. In our study, ~40 % of
cases underwent appendectomies. We found that
an appendectomy had no impact on survival in
mucinous or other types of BOT. Thus, it is not
necessary to perform an appendectomy routinely
in patients with mucinous BOTs, according to our
findings. Kleppe et al.’s and Lin et al.’s studies
reached the same conclusion [16,17].
3) Which type of procedure (radical vs. conservative)
should the surgeon choose in patients with BOTs?
There is an important and controversial issue about
surgical approaches in diagnosed BOT patients,
especially in women who wish to preserve their
reproductive status. Many previous studies [13,18]
have suggested that patients who undergo
Table 3 Clinical details of patients based on age
Age < 40 (n= 353) Age ≥40 (n= 380) Pvalue RR (95 % CI)
Serous histology
a
262 (74.1) 272 (71.6) 0.723
Complete surgery
a
189 (53.5) 206 (54.2) 0.448
Radical surgery
a
184 (52.1) 204 (53.7) 0.673 1.0 (0.7–1.4)
Appendectomy
a
145 (41.1) 144 (37.9) 0.378 1.0 (0.9–1.2)
Stage I
a
311 (88.1) 343 (90.2) 0.782
OS
b
57.7 ± 42.1 52.9 ± 43.4 0.419
DFS
b
53.5 ± 39.7 50.0 ± 40.7 0.390
Recurrence
a
33 (9.3) 36 (9.5) 0.954 0.9 (0.6–1.5)
OS overall survival, DFS disease-free survival
Data are expressed as
a
:n(%),
b
: mean ± standard deviation
Table 4 Results of multivariate analyses of disease-free survival and overall survival
Disease-free survival Overall survival
Hazard ratio 95 % CI Pvalue Hazard ratio 95 % CI Pvalue
Age (<40 vs. ≥40) 1.0 0.8–1.2 0.67 1.0 0.8–1.2 0.61
Stage (I/II vs. III/IV) 0.9 0.9–1.0 0.39 0.9 0.9–1.0 0.86
Radical surgery 1.0 0.9–1.0 0.25 1.0 0.9–1.0 0.64
Staging surgery 1.0 0.9–1.0 0.10 1.0 0.9–1.1 0.052
Menopause 0.9 0.8–1.2 0.95 1.0 0.8–1.3 0.57
Invasive implant 0.8 0.6–1.2 0.47 0.8 0.6–1.2 0.51
Lymph node dissection 0.9 0.9–1.1 0.08 0.8 0.7–1.1 0.08
Adjuvant chemotherapy (tumorstage ≥IC) 0.8 0.6–1.0 0.06 0.9 0.8–1.1 0.07
CI confidence interval
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conservative surgery have higher recurrence rates
than the radical surgery group. Güvenal et al.’s
study showed that patients who underwent radical
surgery had a 3 % recurrence rate, whereas in
patients who underwent fertility sparing surgeries,
the recurrence rate was 8.3 % [13]. Furthermore,
Boran et al. reported that patients who underwent
radical surgery had no recurrence, whereas in
patients who underwent conservative surgery, the
recurrence rate was 6.5 % [18]. In contrast, we
found that the rate of recurrence between the two
groups was not different (35/345, 10.5 % vs. 34/388,
8.7 %; p= 0.405). Furthermore, we found that radical
surgery was not an independent prognostic factor
for DFS or OS. Thus, we considered that performing
radical surgery makes no sense with regard to
recurrence in BOT patients. We attribute these
findings to the follow-up period of our study,
which was much longer than those of other studies
(e.g., Boran et al. and Güvenal et al.). Ayhan et al.,
suggested that patients with BOTs can be treated
safely with conservative surgery [11]. In the present
study, we found that surgical procedure (radical vs.
conservative) was not an independent prognostic
factor for DFS or OS. These findings were similar
to those of previous studies [13,18,19]. We also
demonstrated that hysterectomy had no impact on
survival in BOT patients, similar to Menczer et al.’s
study [20].
4) Should patients with BOTs receive adjuvant
chemotherapy after surgery if they have a tumor
of stage ≥IC, as with epithelial ovarian tumors?
Based on the literature, the use of adjuvant
chemotherapy for BOTs remains controversial.
According to the National Comprehensive
Cancer Network (NCCN), the treatment
recommendation after comprehensive staging
depends on the presence or absence of invasive
implants. The initial therapeutic approach in
patients having invasive implants may include
observation; alternatively, consideration can be
given to treating patients according to the
guidelines for epithelial ovarian cancer
(category 2B for adjuvant chemotherapy) [21].
In the present study, surgery followed by
chemotherapy did not show a different survival
rate compared to no adjuvant chemotherapy in
advanced-stage BOTs. This finding is similar to
that of Trope et al. [22]. Most of the recurrence
patients were treated with surgery alone in our
Table 5 Characteristics of patients based on recurrence
Recurrence
(n= 69)
No recurrence
(n= 664)
Pvalue RR (95 % CI)
Age (years)
a
41.5 ± 13.8 39.0 ± 12.4 0.146
Tumor size (mm)
a
113.5 ± 65.1 93.5 ± 53.8 0.094
Surgery type
b
0.470 0.6 (0.1–2.4)
Laparascopy 2 (5.9) 32 (94.1)
Laparatomy 67 (9.6) 632 (90.4)
Stage
b
0.129 0.6 (0.4–1.1)
≥IC 18 (12.6) 125 (87.4)
< IC 50 (8.5) 540 (91.5)
Radical Surgery
b
0.405 1.2 (0.7–1.9)
Yes 34 (8.8) 354 (91.2)
No 35 (10.2) 310 (89.8)
Data are expressed as
a
: mean ± standard deviation,
b
:n(%)
Table 6 Results of univariate and multivariate analyses of risk factors of patients with recurrent BOTs
Univariate analysis Multivariate analysis
Hazard ratio 95 % CI Pvalue Hazard ratio 95 % CI Pvalue
Age (years)
(<40 vs. ≥40)
1.0 0.6–1.7 0.845 1.1 0.6–1.8 0.877
Stage
(< IC vs. ≥IC)
0.9 0.8–1.0 0.314 0.8 0.7–0.9 0.322
Radical surgery 1.0 0.9–1.1 0.968 1.0 0.9–1.1 0.808
Staging surgery 0.9 0.7–1.2 0.541 0.9 0.6–1.2 0.519
Gokcu et al. Journal of Ovarian Research (2016) 9:66 Page 6 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

study, but we found no significant difference in
DFS or OS in recurrent patients treated with surgery
alone, chemotherapy alone, or sequential treatment.
5) What is the role of frozen section analyses during
BOT surgery? Do the results differ between serous
and mucinous BOTs?
An accurate intraoperative diagnosis is important in
the management of BOTs during the intra- and
postoperative periods. Reported accuracy rates have
varied widely, from 50 to 85 %. In this study, the
accuracy of frozen section analysis was 90.4 %,
slightly higher than many previous studies [23,24].
One reason may be that there were fewer mucinous
tumors in the present study, because mucinous
histology has been reported to be associated with
low sensitivity in frozen section analyses in past
studies [25,26]. Similarly, in the present study, the
accuracy for serous tumors was 94 % versus 80 %
for mucinous tumors (p< 0.001).
6) What should the surgeon do for patients with
recurrent BOTs?
We found no significant difference in DFS or OS
rates in recurrent patients managed with secondary
surgery, chemotherapy, or sequential treatment
(HR = 1.3; 95 % CI = 1.1–1.5; p= 0.410 and
HR = 0.8; 95 % CI = 0.6–1.1; p= 0.856, respectively).
Furthermore we showed that age (<40 vs. ≥40),
FIGO stage (< IC vs. ≥IC), performance of radical
surgery, and performance of surgical staging
(vs. not) were not independent risk factors for
recurrence of BOTs. In contrast, Ren et al. reported
that a conservative surgical procedure was an
independent risk factor for recurrence. Additionally,
Sumin et al. reported that age was an independent
risk factor for recurrence [12,27]. One reason for
these differences may be that our study included
more participants than the other studies.
7) What are the prognostic factors for overall and
disease-free survival in BOTs?
We found that surgical staging (vs. not), FIGO stage,
age (<40 vs. ≥40), menopausal status, the presence
of an invasive implant, radical (vs. conservative)
surgery, lymph node dissection (vs. not), and
undergoing adjuvant CT for a tumor of stage ≥IC
were not independent prognostic factors for DFS
or OS. Our results are similar to many previous
studies [13,14,28]. In addition to our findings,
Güvenal et al. suggested that appendectomy was
not an independent prognostic factor for DFS or OS.
This study has several limitations. First, it was a
retrospective analysis of patients from various institu-
tions. Second, there were many different clinical ap-
proaches. Third, the absence of some data and the
histopathological evaluations of BOTs may vary de-
pending on the experience of the institutions. Despite
these limitations, this study represents one of the largest
series of cases with BOTs, as a 10-center study. Moreover,
the availability of good follow-up data increased the
validity of the results and mitigated the weaknesses.
Conclusions
In conclusion, patients undergoing conservative surgeries
did not have higher recurrence rates, and survival time
was not shortened. Detailed surgical staging, including
lymph node sampling or dissection, appendectomy, and
hysterectomy did not cause any difference in survival
rates. Age and radical surgery were not independent prog-
nostic factors for DFS. Thus, our findings suggest that
radical surgery and comprehensive surgical staging should
not be routinely performed in BOT patients. We believe
that this study shows important findings due to its multi-
centric and long-term nature. Although this study was a
retrospective analysis, we believe that it provides useful
information for prospective randomized controlled trials
in the future.
Abbreviations
BOTs: Borderline ovarian tumors; FIGO: International Federation of Gynecology
and Obstetrics
Acknowledgements
No.
Funding
This paper was written without any funding sources.
Availability of data and materials
All dataset on which the conclusions are based upon are deposited and
presented in the article.
Authors’contributions
All authors contributed to the development of the review, the design of the
figures and in writing the manuscript. OA and KG participated in the design
of the study and performed the statistical analysis. MG,TG, AK, TS, OG, BA,
NC,İAO, LY, MS, GP, ZFC, TT, MMM, RÖ, EA, OE, AT, VG, MSİ, HG, MY, AS, TŞ,
MH, BB, ADU conceived of the study, and participated in its design and
coordination and helped to draft the manuscript. All authors read and
approved the final manuscript.
Competing interests
The authors declare that they have no competing interests.
Consent for publication
Not applicable.
Ethics approval and consent to participate
All subjects have signed informed consents. This study was approved by
Ethics Committee of Tepecik Education and Research Hospital.
Author details
1
Department of Gynecology and Gynecologic Oncology, Izmir Tepecik
Education and Research Hospital, Izmir, Turkey.
2
Department of Gynecology
and Gynecologic Oncology, Mugla SıtkıKocman University Education and
Research Hospital, Mentese 48000, Mugla, Turkey.
3
Department of
Gynecology and Gynecologic Oncology, Sisli Hamidiye Etfal Education and
Research Hospital, Istanbul, Turkey.
4
Department of Gynecology and
Gynecologic Oncology, Zekai Tahir Burak Education and Research Hospital,
Gokcu et al. Journal of Ovarian Research (2016) 9:66 Page 7 of 8
Content courtesy of Springer Nature, terms of use apply. Rights reserved.

Ankara, Turkey.
5
Department of Gynecology and Gynecologic Oncology,
Zeynep Kamil Education and Research Hospital, Istanbul, Turkey.
6
Department of Gynecology and Gynecologic Oncology, Akdeniz University
School of Medicine, Antalya, Turkey.
7
Department of Gynecology and
Gynecologic Oncology, Istanbul Education and Research Hospital, Istanbul,
Turkey.
8
Department of Gynecology and Gynecologic Oncology, Dicle
University School of Medicine, Diyarbakır, Turkey.
9
Department of
Gynecology and Gynecologic Oncology, Bakırköy Dr. Sadi Konuk Education
and Research Hospital, Istanbul, Turkey.
10
Department of Gynecology and
Gynecologic Oncology, Antalya Education and Research Hospital, Antalya,
Turkey.
11
Department of Gynecology and Gynecologic Oncology, Zonguldak
Bulent Ecevit University School of Medicine, Zonguldak, Turkey.
Received: 1 August 2016 Accepted: 9 October 2016
References
1. Taylor H. Malignant and semi-malignant tumors of the ovary. Surg Gynecol
Obstet. 1929;48:204–30.
2. Hart WR, Norris HJ. Borderline and malignant mucinous tumors of the ovary.
Histologic criteria and clinical behavior. Cancer. 1973;31:1031–45.
3. Tinelli R, Tinelli A, Tinelli FG, Cicinelli E, Malvasi A. Conservative surgery for
borderline ovarian tumors: a review. Gynecol Oncol. 2006;100:185–91.
4. Gershenson DM. Clinical management potential tumours of low
malignancy. Best Pract Res Clin Obstet Gynaecol. 2002;16(4):513–27.
5. Medeiros LR, Rosa DD, da Rosa MI, Bozzetti MC. Accuracy of CA 125 in the
diagnosis of ovarian tumors: a quantitative systematic review. Eur J Obstet
Gynecol Reprod Biol. 2009;142(2):99–105.
6. Timmerman D, Van Calster B, Testa AC, Guerriero S, Fischerova D, Lissoni AA,
et al. Ovarian cancer prediction in adnexal masses using ultrasound-based
logistic regression models: a temporal and external validation study by the
IOTA group. Ultrasound Obstet Gynecol. 2010;36(2):226–34.
7. Fauvet R, Boccara J, Dufournet C, David-Montefiore E, Poncelet C, Daraï E.
Restaging surgery for women with borderline ovarian tumors: results of a
French multicenter study. Cancer. 2004;100:1145.
8. Benedet JL, Bender H, Jones 3rd H, Ngan HY, Pecorelli S. FIGO staging
classifications and clinical practice guidelines in the management of
gynecologic cancers. FIGO Committee on Gynecologic Oncology. Int J
Gynaecol Obstet. 2000;70(2):209–62.
9. Gotlieb WH, Chetrit A, Menczer J, Hirsh-Yechezkel G, Lubin F, Friedman E,
et al. Demographic and genetic characteristics of patients with borderline
ovarian tumors as compared to early stage invasive ovarian cancer. Gynecol
Oncol. 2005;97(3):780–3.
10. Romagnolo C, Gadducci A, Sartori E, Zola P, Maggino T. Management of
borderline ovarian tumors: results of an Italian multicenter study. Gynecol
Oncol. 2006;101(2):255–60.
11. Ayhan A, Guvendag Guven ES, Guven S, Kucukali T. Recurrence and prognostic
factors in borderline ovarian tumors. Gynecol Oncol. 2005;98(3):439–45.
12. Ren J, Peng Z, Yang K. A clinicopathologic multivariate analysis affecting
recurrence of borderline ovarian tumors. Gynecol Oncol. 2008;110(2):162–7.
13. Guvenal T, Dursun P, Hasdemir PS, Hanhan M, Guven S, Yetimalar H, et al.
Effect of surgical staging on 539 patients with borderline ovarian tumors: a
Turkish Gynecologic Oncology Group study. Gynecol Oncol. 2013;131(3):
546–50.
14. Winter WE, Kucera PR, Rodgers W, McBroom J, Olsen C, Maxwell L. Surgical
staging in patients with ovarian tumours of low malignant potential. Obstet
Gynecol. 2002;100:671–6.
15. Tinelli R, Malzoni M, Cosentino F, Perone C, Tinelli A, Malvasi A, Cicinelli E.
Feasibility, safety, and efficacy of conservative laparoscopic treatment of
borderline ovarian tumors. Fertil Steril. 2009;92(2):736–41.
16. Kleppe M, Bruls J, Van Gorp T, Massuger L, Slangen BF, Van de Vijver KK,
et al. Mucinous borderline tumours of the ovary and the appendix: a
retrospective study and overview of the literature. Gynecol Oncol. 2014;
133(2):155–8.
17. Lin JE, Seo S, Kushner DM, Rose SL. The role of appendectomy for
mucinous ovarian neoplasms. Am J Obstet Gynecol. 2013;208(46):e1–4.
18. Boran N, Cil AP, Tulunay G, Ozturkoglu E, Koc S, Bulbul D, et al. Fertility and
recurrence results of conservative surgery for borderline ovarian tumors.
Gynecol Oncol. 2005;97:845.
19. Gungor T, Cetinkaya N, Yalcin H, Ozdal B, Ozgu E, Baser E, et al.
Retrospective evaluation of borderline ovarian tumors: single center
experience of 183 cases. Arch Gynecol Obstet. 2015;291(1):123–30.
20. Menczer J, Chetrit A, Sadetzki S, Anderma S, Alteras M, Anteby S, et al. The
effect of hysterectomy on survival of patients with borderline ovarian
tumors. Gynecol Oncol. 2012;125(2):372–5.
21. NCCN. Clinical Practice Guidelines in Oncology Ovarian Cancer. Including
Fallopian Tube Cancer and Primary Peritoneal Cancer Version 2. 2015.
22. Trope CG, Kaern J, Davidson B. Borderline ovarian tumours. Best Pract Res
Clin Obstet Gynaecol. 2013;26(3):325–36.
23. Ilvan S, Ramazanoglu R, Ulker Akyildiz E, Calay Z, Bese T, Oruc N. The
accuracy of frozen section (intraoperative consultation) in the diagnosis of
ovarian masses. Gynecol Oncol. 2005;97(2):395–9.
24. Shih KK, Garg K, Soslow RA, Chi DS, Abu-Rustum NR, Barakat RR. Accuracy of
frozen section diagnosis of ovarian borderline tumor. Gynecol Oncol. 2011;
123(3):517–21.
25. Tempfer CB, Polterauer S, Bentz EK, Reinthaller A, Hefler LA. Accuracy of
intraoperative frozen section analysis in borderline tumors of the ovary: a
retrospective analysis of 96 cases and review of the literature. Gynecol
Oncol. 2007;107(2):248–52.
26. Pongsuvareeyakul T, Khunamornpong S, Settakorn J, Sukpan K, Suprasert P,
Siriaunkgul S. Accuracy of frozen—section diagnosis of ovarian mucinous
tumors. Int J Gynecol Cancer. 2012;22:400–6.
27. Oh S, Kim R, Lee YK, Kim JW, Park NH, Song YS. Clinicopathological aspects
of patients with recurrence of borderline ovarian tumors. Obstet Gynecol
Sci. 2015;58(2):98–105.
28. Desfeux P, Camatte S, Chatellier G, Blanc B, Querleu D, Lécuru F. Impact of
surgical approach on the management of macroscopic early ovarian
borderline tumors. Gynecol Oncol. 2005;98(3):390–5.
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