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European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 189–194
Contents lists available at ScienceDirect
European Journal of Obste
Reproductiv
journal homepage: www.e lDepartment of Pathology, Ludwig-Maximilians-University Munich, Campus Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany
dDepartment of Obstetrics and Gynecology, Kiel University Hospital, Michaelisstrasse 16, 24105 Kiel, Germany
1. Introduction
The borderline tumor of the ovary (BOT) accounts for 10–20% of
epithelial ovarian tumors [1]. BOT and invasive carcinomas show
differences in their genetic aberrations suggesting that invasive
tumors of high grade do not arise from pre-existing borderline
lesions [2]. BOT has an incidence of 4.8/100,000 per year [3] and
generally occurs 10 years earlier than ovarian cancer. About a third
of patients are diagnosed under the age of 40. It has been
recognized that the preservation of fertility is of great importance,
especially in young patients [4]. During the last decades, operative
management of BOT has changed with regard to radicality [5].
Historically, BOT had been described as a precursor malignancy of
ovarian cancer and was consequentially operated in the same way
to avoid recurrent invasive disease [6]. Over the years many
studies have shown that a radical operative treatment including
lymphadenectomy is not superior in terms of relapse or survival
[7]. Further investigations have postulated even fertility sparing
surgery to be appropriate in women at childbearing age, especially
when diagnosed at an early stage of disease [8].
In this retrospective study we analyze risk factors for long-term
survival and relapse in patients diagnosed with a borderline tumor
of the ovary (BOT) with special focus on the surgical approach.
2. Materials and methods
All women diagnosed and treated for BOT at our institution
between 1983 and 2006 were included in this retrospective study.
A R T I C L E I N F O
Article history:
Received 16 August 2008
Received in revised form 20 March 2009
Accepted 27 April 2009
Keywords:
Ovarian borderline tumor
Fertility sparing surgery
Laparoscopy
A B S T R A C T
Objectives: To assess long-term survival and relapse rate of patients diagnosedwith a borderline tumor of
the ovary (BOT) with special focus on the influence of primary surgery.
Study design: All women diagnosed and treated for BOT between 1983 and 2006 at our institution were
included in this retrospective study. Clinical data including operative procedure, stage and histology at
first diagnosis as well as follow-up data were analyzedwith reference to survival times and relapse rates.
Results: Altogether 113 patients could be identified, including 19 women treated with fertility sparing
surgery (19.2%). Mean follow-up time was 9.6  6.6 years. Relapse occurred during the follow-up period in
10 patients (10.1%) with a mean time to recurrence of 2.0  1.7 years. Patients with recurrent disease had a
statistically significantly worse survival: 5- and 10-year survival rates were 90.0 and 80.0% compared with
98.9 and 94.4% for those without (p = 0.0208), respectively. Relapse rate was 7.1% in early borderline patients
(Ia: 4/56) and 14% (>Ia: 6/43) for all others (p = 0.436). Patients with invasive implants had a statistically
significantly higher relapse rate (p = 0.0112). No significant difference in relapse rates or survival was
observed between the histological subtypes. Five- and 10-year survival rates of women treated with fertility
sparing surgery (n = 19) were 100% and thus not worse than those of radically operated patients (5- and 10-
year survival 95.1 and 90.1%). Relapse rates in both groups were comparable with 10.5 and 10.0% (p = 0.723).
The surgical procedure with lymphadenectomy vs. without had no influence on relapse or survival, neither
did laparoscopy vs. laparotomy.
Conclusion: Our findings confirm the good prognosis of BOT in general. Patients with invasive implants
have higher relapse rates. Fertility sparing surgery in women at childbearing age can be an adequate
treatment option in early stage disease.
 2009 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: Department of Obstetrics and Gynecology, Ludwig-
Maximilians-University Munich, Campus Grosshadern, Marchioninistrasse 15,
80337 Munich, Germany. Tel.: +49 89 7095 6725; fax: +49 89 7095 6724.
E-mail address: Miriam.Lenhard@med.uni-muenchen.de (M.S. Lenhard).
0301-2115/$ – see front matter  2009 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.ejogrb.2009.04.031Long-term follow-up after ovarian bord
large patient cohort
Miriam S. Lenhard a,*, Stefanie Mitterer a, Carolin K
Klaus Friese a, Alexander Burges a
aDepartment of Obstetrics and Gynecology, Ludwig-Maximilians-University Munich, C
bDepartment of Clinical Chemistry, Ludwig-Maximilians-University Munich, Campus G
cline tumor: Relapse and survival in a
per d, Petra Stieber b, Doris Mayr c, Nina Ditsch a,
us Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany
hadern, Marchioninistrasse 15, 81377 Munich, Germany
trics & Gynecology and
e Biology
sev ier .com/ locate /e jogrb

3.1. Relapse and survival
Of all patients, 10 died during follow-up time. One death is
known to be tumor-associated. Mean survival time of the patients
who died was 7.7  4.2 years (range 2–14 years). The general 5- and
10-year survival rates were 98.0 and 92.9%, respectively.
Altogether, relapse occurred during the follow-up period in 10
patients (10.1%, 10/99) with a mean time to recurrence of 2.0  1.7
years (range 0.3–6.2 years). In six of the patients relapsewas detected
by sonography, in two by clinical symptoms and in two by CA-125
elevation. Patients with recurrent disease had a statistically
significantly worse survival rate compared with those without: 5-
and 10-year survival were 90.0 and 80.0% (patients with relapse) vs.
Postmenopausal 57 0 57
Menarche (years) 13.4 13.0 13.5
Tumor marker CA-125 U/ml (mean) 128.0 55.1 142.8
Histology
Serous 73 14 59
Mucinous 39 5 34
Endometroid 1 0 1
Stage by FIGO
Ia 63 12 51
Ib 13 0 13
Ic 18 5 13
IIa 3 0 3
IIb 3 0 3
IIc 1 0 1
IIIa 10 1 9
IIIb 1 0 1
IIIc 1 1 0
IV 0 0 0
Cytology
Positive 5 0 5
Negative 108 19 89
Implants 19 3 16
Invasive 11 1 10
Non-invasive 8 2 6
None 94 16 78
Laterality
Left 38 9 29
Right 44 9 35
Bilateral 20 1 19
NA 11 0 11
Surgical approach
Laparoscopy 18 4 14
Laparotomy 95 15 80
Lymph-node sampling
Done 35 1 34
Not done 89 18 61
Second-look surgery 12 3 9
Adjuvant chemotherapy 10 1 9
Relapse 10 2 8
Death 10 0 10
M.S. Lenhard et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 145 (2009) 189–194190Clinical data, demographic, diagnostic and treatment informa-
tion were primarily collected from the patients’ charts. Patients
were seen at 3-month intervals after initial diagnosis for a 2-
year period, thereafter at 6-month intervals for another 2 years
and then once a year to evaluate for sonographic and clinical
signs of relapse. The patients’ data were further reviewed for the
surgical procedure performed. Radicality varying from unilateral
adnexectomy, in this study referred to as fertility sparing
surgery, to hysterectomy with bilateral adnexectomy, omen-
tectomy and lymphadenectomy were recorded. Bilateral adnex-
ectomy, hysterectomy, omentectomy, cytology, and several
peritoneal biopsies were regarded as full staging. Tumor typing
and staging were performed by the department of pathology
according to the criteria of the International Federation of
Gynaecologists and Obstetricians (FIGO) and the International
Union against Cancer (IUCC).
The following parameters were registered for each patient: age
at primary diagnosis, menopausal stage, age at menopause,
surgical procedure performed, tumor type and stage. Also, the
presence of BOT cells in ascites was recorded. In follow-up, the
occurrence of relapse, time to relapse, death and survival time
were registered. The main outcomes assessed were disease
recurrence and survival.
Statistical analysis was performed using MedCalc (Version
8.1; MedCalc Software, Mariakerke, Belgium). All values are
given as mean and standard deviation. To test differences
between continuous variables for statistical significance, the
Mann–Whitney test for unpaired variables was applied. For
categorical data, the chi-square test was used. For the
comparison of survival times, Kaplan–Meier curves were drawn
for different patient groups. The chi-square statistic of the log-
rank test was calculated to test differences between survival
curves for significance. p values less than 0.05 were considered
as statistically significant.
3. Results
Altogether, 113 patients could be identified, including 19
women with fertility sparing surgery. Mean follow-up time was
9.6  6.6 years (minimum 6 months, maximum 23.5 years, median
7.9 years). Mean age at primary diagnosis was 51.2  16.6 years;
altogether 36 women (32%, 36/113) were under the age of 40. About
half of the patients were premenopausal (56/113). Histology revealed
a serous tumor in 73 women (64.6%), mucinous in 39 (34.5%) and
endometrioid in one case (0.9%). 63 patients (55.8%) were diagnosed
at FIGO stage Ia, 13 (11.5%) at stage Ib, 18 (15.9%) at stage Ic, 7 (6.3%)
at stage II and 12 (10.6%) at stage III (Table 1). Cytology was positive
for tumor cells in five cases (4.4%, 5/113). Implants were found in 19
patients: 11 were invasive (57.9%) and 8 non-invasive implants
(42.1%). Localization of implants was the omentum (42.1%), the
peritoneum (31.6%), diaphragm (10.5%) and bladder (10.5%). The
mesosalpinx, uterus, umbilicus and kidney were affected in less
than 10%.
An adjuvant platinum-based chemotherapy was recommended
to 11 patients diagnosed with invasive implants. Only one patient
did not follow this treatment recommendation.
Lymphadenectomy was performed in 35 cases (30.9%, 35/113).
The surgical approach was laparoscopic in 15.9% (18/113), and no
conversion from laparoscopic to laparotomic approach occurred.
All patients had been staged by multiple peritoneal biopsies and
cytology. In 74% (n = 84/113) an omentectomywas performed, and
only 15.4% (n = 6/39) of all patients withmucinous tumors had had
appendectomy, resulting in a complete operative staging in 76.1%
(86/113) of all patients. Second-look surgery was chosen in 12
cases (10.6%, 12/113), never revealing macroscopic or microscopic
tumor tissue (Table 1).Table 1
Patient and tumor related characteristics for all patients, fertility sparing operated
patients and radical operated patients, NA = not applicable.
Total Fertility sparing Radical surgery
Total number of patients 113 19 94
Age at primary diagnosis (years) 51.2 34.2 54.7
Age at diagnosis (years)
<40 36 17 19
40 77 2 75
BMI (kg/m2) 24.8 23.5 25.1
Menopause status
Premenopausal 56 19 37