Fertility-sparing surgery for ovarian low malignant potential tumors
Gautam G. Raoa, Elizabeth N. Skinnerb, Paola A. Gehrigb, Linda R. Duskac,
David S. Millera, John O. Schorgea,*
aDivision of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center,
5323 Harry Hines Boulevard, J7.124, Dallas, TX 75390-9032, USA
bUniversity of North Carolina School of Medicine, Chapel Hill, NC 27599, USA
cHarvard Medical School-Massachusetts General Hospital, Boston, MA 02115, USA
Received 12 January 2005
Available online 16 June 2005
Objective. Ovarian low malignant potential (LMP) tumors have an excellent prognosis when treated by surgical resection. Conservative
management usually involves leaving behind the uterus and contralateral adnexa to allow future childbearing. The purpose of this study was
to determine the outcome of women treated with fertility-sparing surgery.
Methods. All patients diagnosed with ovarian LMP tumors between 1984 and 2003 were identified at three institutions. Data were
retrospectively extracted from clinical records.
Results. Thirty-eight (15%) of 249 women with LMP tumors underwent fertility-sparing surgery. Twenty-three were nulliparous and four
primiparous. Thirty-three (87%) underwent unilateral salpingo-ophorectomy and five (13%) cystectomy. Fourteen patients also had
contralateral cystectomy or biopsy. Thirty-four (89%) were stage I, one (3%) stage II and three (8%) stage III. Most tumors had serous (55%)
or mucinous (42%) histology. No patients received adjuvant therapy. Six (16%) of 38 recurred after a median follow-up of 26 months: five in
the remaining ovary were salvaged with surgical resection alone, and none died from recurrent LMP tumor. Five women delivered six term
infants during post-treatment surveillance.
Conclusion. Fertility-sparing surgery for ovarian LMP tumors is an option for motivated patients. Preservation of the contralateral adnexa
increases the risk of recurrence, but surgical resection is usually curative.
D 2005 Elsevier Inc. All rights reserved.
Keywords: Fertility-sparing surgery; Ovarian borderline tumor
Low malignant potential (LMP) tumors account for
approximately 15% of all epithelial ovarian cancers .
These neoplasms have histologic and biologic features that
are intermediate to those of clearly benign and frankly
malignant ovarian tumors. Criteria for making the diagnosis
include the presence of nuclear atypia, stratification of the
epithelium, formation of microscopic papillary projections
and minimal or absent stromal invasion. Patients with
ovarian LMP tumors have a 10-year survival rate of 95%
. Complete resection by hysterectomy and bilateral
salpingo-oophorectomy is the standard treatment.
Fertility-sparing surgery may be an option for selected
patients [3–8]. Leaving behind the uterus and contralateral
adnexa increases the risk of disease recurrence due to the
possibility of bilateral synchronous tumors or occult
metastases [4,5,8]. Since the majority of women are
diagnosed with ovarian LMP tumors during their repro-
ductive years, many are willing to accept additional risk to
maintain their fertility. Trimble et al. observed that half of
women less than 40 years of age underwent fertility-
sparing surgery . The risk of a new primary lesion/
recurrence after conservative management ranges from 0–
19% [3–8]. Presumably, complete resection would have
prevented most of these events.
0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
* Corresponding author. Fax: +1 214 648 8404.
E-mail address: email@example.com (J.O. Schorge).
Gynecologic Oncology 98 (2005) 263 – 266
Younger nulliparous women are more likely to undergo
fertility-sparing surgery. However, little is known about
racial/ethnic disparity or other factors that may affect the
management decision. Contralateral ovarian biopsy or
cystectomy is not routinely advocated at the time of surgery
unless there is a visible abnormality, but there are few
alternatives to identify patients with occult disease. The
purpose of this study was to determine the outcome of
women treated with fertility-sparing surgery for ovarian
Materials and methods
Institutional Review Board approval was obtained at the
University of Texas Southwestern Medical Center, Univer-
sity of North Carolina School of Medicine-Chapel Hill and
Harvard Medical School-Massachusetts General Hospital.
The Society of Gynecologic Oncology Database and
hospital tumor registries were searched to identify all
women diagnosed with ovarian LMP tumors between
January 1984 and June 2003.
Medical records were reviewed for data extraction.
Patient age, racial/ethnic group, gravidity, parity, preopera-
tive CA125, histology, tumor size, stage, presence of
microinvasion, type of primary surgery, staging procedures
performed, location and number of resected lymph nodes,
length of postoperative hospital stay, estimated blood loss,
location of metastases, type of adjuvant therapy, duration of
follow-up and development of disease recurrence or death
were recorded. Fertility-sparing surgery was defined as any
procedure in which the uterus and at least some ovarian
tissues were left intact. Women who underwent fertility-
sparing surgery were compared to those who underwent
more extirpative surgery .
Categorical variable comparisons were conducted by
Chi-square and Fisher’s Exact Tests. Continuous variables
were evaluated for normality by the Shapiro–Wilk (W)
statistic. If normality was assured, parametric comparisons
were compared by analysis of variance (ANOVA) and
Student’s t test. Non-normally distributed continuous
variables were compared with the Mann–Whitney U
statistic and Kruskal–Wallis. Evaluation of independent
factors predicting disease-specific recurrence was conducted
by nominal logistic regression analysis. Two-sided P values
are reported with the alpha for all tests set at 0.05. Statistical
analysis was performed with SPSS version 12.0 software
(SPSS, Inc., Chicago, IL).
Thirty-eight (15%) of 249 women underwent fertility-
sparing surgery for ovarian LMP tumors. The age at
diagnosis (median 26 years, range: 15–39), gravidity and
parity were lower than those who underwent complete
resection (each P < 0.001; Table 1). Twenty-three
patients were nulliparous and four primiparous. The
frequency of conservative management varied by racial/
ethnic group (P = 0.002) and histologic type (P = 0.02),
but not institution (P = 0.60). In this cohort, more
Hispanics (47%) and Asians (67%) were younger than 40
years compared to White (27%) and Black women (35%;
P = 0.01).
Surgical staging was performed in 184 patients and 65
were clinically staged. Women in the fertility-sparing group
were less likely to undergo surgical staging (P = 0.04) and
had a lower estimated blood loss (P < 0.001). Thirty-four
(17%) of 196 stage I patients underwent fertility-sparing
surgery versus 4 (8%) of 53 stage II–III patients (P = 0.21).
None of the 38 patients with ovarian LMP tumors received
Fertility-sparing surgery primarily involved unilateral
salpingo-ophorectomy (USO) in 33 (87%) patients. Six
underwent concomitant contralateral ovarian cystectomy
and had no evidence of malignancy. Four others had biopsy
of the contralateral ovary at the time of primary surgery
without suggestion of a grossly visible abnormality. Serous
LMP tumor identical to the primary tumor was diagnosed in
Characteristics of women undergoing fertility-sparing surgery for ovarian
n = 38
n = 211
Median age at diagnosis (y)
Racial/ethnic group, n (%)
Mean CA-125 (mIU/ml)
Mean tumor size (cm)
Presence of microinvasion, n (%)
FIGO stage, n (%)
Histologic type, n (%)
Institution, n (%)
Surgical staging, n (%)
Median estimated blood
Median hospital stay (d)
Median follow-up (mo)
Disease recurrence, n (%)
G.G. Rao et al. / Gynecologic Oncology 98 (2005) 263–266
one; three revealed benign ovarian tissue. Five (13%)
women underwent ovarian cystectomy as their primary
treatment. Four of these procedures were performed
Six (16%) of 38 patients recurred (Table 2). Five in the
contralateral ovary were salvaged by surgical resection.
One patient initially surgical stage IIIA was diagnosed with
recurrent disease by malignant peritoneal cytology at the
time of laparoscopy for pelvic pain. She did not receive
further treatment and remains clinically free of disease.
Age, tumor size, histology, presence of microinvasion,
surgical staging, stage and type of fertility-sparing surgery
(USO v cystectomy) were not associated with disease
recurrence by multivariate analysis (all P = NS). None of
the women managed conservatively died from recurrent
Three women were inadvertently diagnosed with primary
LMP tumor at the time of surgery for an ectopic pregnancy
when a suspicious ovarian mass was intraoperatively noted.
Two patients underwent exploration for an adnexal mass
during pregnancy (14 and 18 weeks gestation). Each had
USO with surgical staging and subsequently delivered at
term. Three additional women had a total of four gestations
during post-treatment surveillance. All resulted in term
deliveries. None of the 38 patients developed a pregnancy-
related complication during follow-up that was attributable
to prior surgery.
Fertility-sparing surgery for LMP tumors is an option for
motivated patients. Disease-related deaths appear to be very
rare [3–8]. Zanetta et al. prospectively followed 189
conservatively treated women at the University of Milano.
One woman with a stage IC mucinous LMP tumor under-
went unilateral ovarian cystectomy and a few months
postoperatively developed diffuse progression of invasive
carcinoma. She quickly succumbed despite aggressive
surgery and chemotherapy . Primary hysterectomy and
bilateral salpingo-oophorectomy or even USO might have
prevented this patient death. None of the 38 women in our
study of conservative managed ovarian LMP tumors died
from disease. We advocate careful preoperative counseling
for adnexal masses. Age, parity and desire for future fertility
should be discussed so that the patient and surgeon have a
clear understanding of the surgical plan in the event ovarian
LMP tumor is intraoperatively diagnosed.
Preservation of functional ovarian tissue increases the
risk of recurrence, but surgical resection alone is usually
curative [4–8]. Zanetta et al. reported a higher rate of
disease recurrence in women undergoing fertility-sparing
surgery (19% v 5%) compared to 150 patients managed by
more radical surgery. Thirty-one of 35 recurring in the
contralateral ovary or in the same ovary after cystectomy
were salvaged with repeat surgery alone . We observed a
16% rate of disease recurrence compared to 4% when
complete resection was performed. Five of six patients who
recurred were managed by complete resection, and all
remain free of disease. Interestingly, one patient in our study
had serous LMP detected by contralateral ovarian biopsy
without visible abnormality. We speculate that this proce-
dure would be of low yield, but there are few other options
for ruling out contralateral disease at the time of surgery.
Transvaginal ultrasound may be the most effective diag-
nostic technique for the follow-up of conservatively
managed patients .
Fewer fertility-sparing patients underwent surgical
staging. We speculate that there was less preoperative
clinical suspicion of malignancy in these younger women.
In addition, ovarian mucinous LMP tumors were more
than twice as common and are especially prone to
misinterpretation at frozen section [11–13]. Aggressive
surgical staging is of limited value in patients with
mucinous histology because virtually all behave in a
clinically benign fashion without metastases [9,14–16].
The inability to reliably exclude stromal invasion at the
time of intraoperative frozen section is a recognized
limitation in managing LMP tumors, but fortunately, the
long-term survival of patients with stage I invasive
epithelial ovarian cancer preserving fertility is also
excellent [9,11,17,18]. Re-operation for surgical staging
after fertility-sparing surgery is hard to justify when the
final pathologic diagnosis suggests LMP tumor confined
to a single ovary . We advocate complete resection for
all LMP patients at the completion of childbearing based
on our finding of a higher risk of recurrence—regardless
Characteristics of women who recurred after fertility-sparing surgery for ovarian LMP tumors
No. Age RaceG/PInitial surgery Histology StageSurgically
LSO, right ovarian biopsy
LSO, right ovarian cystectomy
LSO, right ovarian cystectomy
RSO, left ovarian cystectomy
G.G. Rao et al. / Gynecologic Oncology 98 (2005) 263–266
Hispanic and Asian women were more likely than Download full-text
White or Black women to undergo fertility-sparing surgery.
This observation chiefly reflects the age of each group in
our sample. However, we cannot discount the possibility
that Hispanic and Asian women have a heightened sense
of anxiety to maintain their fertility despite the diagnosis
of a malignant ovarian tumor. Alternatively, White and
Black women may be more fearful of any cancer diagnosis
and be willing to forgo future fertility in order to receive
more definitive treatment. In our multiethnic population,
the frequency of fertility-sparing surgery was remarkably
consistent between the three geographically separate
institutions. This topic warrants further investigation.
Patients undergoing fertility-sparing surgery often have
healthy term infants during post-treatment surveillance.
Zanetta et al. reported that 41 of their 189 conservatively
managed patients delivered. Success rates vary by institu-
tion and duration of follow-up [3–8,19]. Five women in our
study subsequently delivered six term infants. We did not
observe an increased risk of ectopic pregnancy or other
surgery-related complication. The diagnosis of ovarian LMP
should not preclude consideration of in vitro fertilization
when necessary to achieve pregnancy .
The findings of this study are limited by the
retrospective data acquisition, relatively short follow-up
and lack of central pathology review. However, Zanetta et
al. found similar findings with a prospective study
design, median follow-up of 70 months and central
pathology review . We believe that including cases
from three geographically separated institutions should
dilute this effect and make our findings broadly
applicable to clinical practice.
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