REVIEW

CURRENT
OPINION Current controversies in the management of germ
cell ovarian tumours
Ignacio Vazquez and Gordon J.S. Rustin

Purpose of review
Fewer than 70 new cases of malignant ovarian germ cell tumours (MOGCTs) are seen each year in the
UK. Because of their rarity, no randomized trials have been reported and many of the advances in
management have arisen from adopting practices developed for managing male germ cell tumours (GCTs).
Not surprisingly, there have been few important publications related to ovarian germ cell tumuors over the
past 2 years. We have therefore included some relevant male germ cell publications. The area in which
there is greatest variability in practice globally is in the proportion of patients with stage 1a disease who go
on surveillance rather than receiving adjuvant chemotherapy. Although there is increasing agreement about
the best management of ovarian GCTs amongst those who treat more than five per year, many patients are
still treated by doctors who usually manage epithelial ovarian cancer but rarely see these patients.
Recent findings
Novel biomarkers including microRNA profiles and DICER1 mutations, identify potential diagnostic and
therapeutic targets in this group of tumours. The role of KIT mutation and amplification in the development
of ovarian dysgerminoma and the use of Sunitinib, a receptor tyrosine kinase inhibitor with an effect on
vascular endothelial growth factor, platelet-derived growth factor and KIT receptors in patients with
platinum-resistant GCT, are novel promising approaches.
Summary
We will therefore highlight some key differences in management of epithelial and germ cell ovarian
tumours.
Keywords
biological markers, novel therapies, ovarian germ cell, surgery, surveillance

INTRODUCTION The peak incidence of MOGCT occurs in girls in

Malignant ovarian germ cell tumours (MOGCTs)
and trophoblastic tumours are at present the only
gynaecological malignancies in which with the
current technologies, we could expect high com-
plete cure rates regardless of the stage at presen-
tation. They account for less than 5% of ovarian
tumours, but precisely because of their high com-
plete cure rates, it is of extreme relevance to always
consider these cancers in the differential diagnosis
of a pelvic mass, more particularly in young women.
Given the fact that MOGCT that contain yolk sac or
trophoblastic elements may have a very short
tumour marker and volume-doubling time, poten-
tially of just a few days, it is essential that diagnosis
and treatment are not delayed. Grossly elevated
levels of alpha-fetoprotein (AFP) and or beta human
chorionic gonadotrophin (b-HCG) in the absence of
pregnancy can be sufficient evidence to start chemo-
therapy in patients with radiological evidence of
advanced disease.
their mid to late teens. Dysgerminomas, either pure
or mixed, are the most frequently occurring
MOGCT, and compared with nondysgerminomas,
they are more likely to present as stage I and be
bilateral. Immature teratomas and yolk sac tumours
are the most frequently occurring nondysgermi-
nomas. Dysgerminomas and nondysgerminomas
in some respects resemble their male germ cell
counterparts, seminomas and nonseminomas. The
far more common dermoid cysts, which are mature
cystic teratomas, are benign ovarian tumours that
can rarely transform to a malignant epithelial
Mount Vernon Cancer Centre, Northwood, Middlesex HA62RN, UK
Correspondence to Gordon J.S. Rustin, Mount Vernon Cancer Centre,
Northwood, Middlesex HA6 2RN, UK. Tel: +44 1923844190; fax: +44
1923844840; e-mail: grustin@nhs.net
Curr Opin Oncol 2013, 25:539–545
DOI:10.1097/01.cco.0000432609.39293.77

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 Gynecologic cancer

Table 1. Frequency of malignant ovarian germ cell

KEY POINTS
tumours

MOGCTs are rare but curable cancers, even Primitive GCTs Frequency of
when advanced. MOGCT

MicroRNAs, nonprotein-coding RNAs are Dysgerminoma 32.8%

overexpressed regardless of histologic subtype in GCTs Yolk sac tumour 15%
and are potential new markers. Polyembryoma –

The primary management for stage I MOGCT should
be fertility sparing surgery with complete staging,
including omentectomy, peritoneal washings and
peritoneal biopsies.

An intensive surveillance schedule is presented, which
should be the standard postsurgical management for
Stage Ia MOGCTs, provided patients can
be compliant.
tumour. The natural history, presentation and
management of MOGCT are significantly different
from epithelial ovarian tumours.
CLASSIFICATION OF OVARIAN GERM
CELL TUMOURS
Histologically, as described in Table 1 [1], MOGCT
are categorized into three main subdivisions,
primitive GCTs, biphasic and triphasic teratomas
and monodermal teratomas and somatic type
tumours associated with biphasic and triphasic
teratomas.
BIOMARKERS
With the current technology available, there is
no universal biomarker for the wide spectrum of
GCT. The serum markers AFP and human chorionic
gonadotropin are currently the most valuable tools
for initial diagnosis and early relapse detection.
However, their intrinsic value is restricted, as
they are not raised in the entire GCT spectrum. In
addition, they can be found elevated in the absence
of malignancy, in pregnancy and in the neonatal
period [2]. Recent investigation by Palmer et al. [3],
and supported by the Murray data discussed below
[4], identified the diagnostic potential of the micro-
RNAs (miRNAs), short, nonprotein-coding RNAs,
which have a significant role in the regulation of
gene expression [5]. Despite the assumption that all
MOGCT originate from primordial germ cells, a
common biological abnormality is yet to be encoun-
tered. Palmer et al. [3] profiled 615 miRNAs in 48
samples from male and female paediatric malignant
GCT and used controls from normal gonad speci-
mens and adult GCT cell lines. The most significant
differentially expressed miRNAs in malignant GCTs
Embryonal carcinoma 4.1%
Non gestational choriocarcinoma 2.1%
Biphasic or triphasic teratoma
Immature teratoma 35.6%
Solid mature teratoma 2.6%
Cystic mature teratoma (dermoid cyst) Not/Applicable
Monodermal teratoma and somatic <1%
tumour associated with biphasic
or triphasic teratoma
Carcinoid
Thyroid group
Sarcoma
Melanocytic
Neuroectodermal tumours
Dysgerminomas, immature teratomas, Mixed GCTs
yolk sac and mixed cell type formed 5.3%
make up over 90% of MOGCT
GCTs, germ cell tumours; MOGCT, malignant ovarian germ cell tumour.
Modified with from [1].
were all from the miR-371–373 and miR-302 clusters
(adjusted P < 0.00005), which were overexpressed
regardless of histologic subtype (yolk sac tumour
seminoma/embryonal carcinoma), site (gonadal/
extragonadal) or patient age (paediatric/adult).
These overexpressed clusters coordinately down-
regulate mRNAs involved in pathways of biological
value.
In an attempt to translate these results clinically,
Murray et al. [4] described a detailed PCR protocol
potentially reproducible in the general popula-
tion. They showed that eight main members of
the miR-371-373 and miR-302 clusters were elevated
in the serum of a 4-year-old boy diagnosed with a
yolk sac tumour, which returned to normal levels
after successful treatment.
If these miRNAs are shown to be elevated in the
majority of patients with GCTs, they could be of
great value in diagnosis and surveillance strategies,
and could enable novel therapeutic approaches that
target fundamental abnormalities of malignant GCT
cells.
&
Alireza et al. [6 ], from David Huntsman’s group,
have recently reported somatic missense mutations
affecting the RNase IIIb domain of DICER1 in non-
epithelial ovarian tumours. Although they were
most commonly seen in Leydig cell tumours, there

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 Management of germ cell ovarian tumours Vazquez and Rustin
were mutations seen in two yolk sac tumours. It will
be interesting to see if patients with this mutation
have a different prognosis to those without this
mutation.
&
Most recently, Chieffi and Chieffi [7 ] in a
systematic review of biomarkers in the different sub-
groups of testicular GCT (TGCT) have postulated that
the different therapeutic outcome of the different
TGCT might be explained by properties of the
gonocytic cells from which the testicular neoplasia
originates. Different biomarkers, including OCT3/
OCT4, SOX2, SOX17, HMGA1, HMGA2, PATZ1,
GPR30, Aurora B, oestrogen receptor b, etc, have
currently being researched in order to discriminate
between histological subgroups and serve as a lead in
future therapeutic approaches for the treatment of
TGCTs.
Targeted therapies
In recent years, the advent of targeted therapies has
accounted for a small revolution in the treatment of a
number of different tumour types. Such impact has
not been translated into the management of GCT,
however. Some efforts have been made to identify
potential therapeutic targets in this group of
tumours. Cheng et al. [8] discuss the role of KIT
mutation and amplification in the development of
ovarian dysgerminoma. In a study of 22 dysgermi-
noma patients, they found six carriers of the exon
17 codon 816 mutations, a figure that is similar (30%)
to the rate of mutations in the seminoma, the
male sex germ cell counterpart to the ovarian dys-
germinoma [9]. Interestingly, KIT mutation was
strongly and significantly associated (P ¼ 0.045)
with advanced pathological stage (67%, four out
of six, were stage 3) but not associated with other
parameters, namely age, tumour size or tumour
bilateralism.
The impact of targeting KIT mutations remains
unclear, as does the role of KIT in the pathogenesis
of dysgerminoma and whether exon 17 KIT
mutations may predict aggressive and chemother-
apy-resistant behaviour of dysgerminomas. This has
been suggested by a case report of Pauls et al. [10] in
which the existence of KIT codon 816 mutation was
associated with an aggressive and platinum-resistant
dysgerminoma in a 14-year-old patient.
Another challenge that clinicians face is that a
subgroup of patients with GCT develop platinum
resistance. On the basis of preliminary studies from
the 1990s that suggest that vascular endothelial
growth factor (VEGF) may play an important role
in development and metastasis of GCT and the fact
that substantially higher VEGF and platelet-derived
growth factor (PDGF) expression has been found in
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patients with GCT compared with normal testis
tissue, VEGF and PDGF expression are suggested
players with an important role in tumour angio-
genesis, tumour progression and metastases.
Oeschle et al. [11] report the preclinical and clinical
activity of Sunitinib, a receptor tyrosine kinase
inhibitor with effect in VEGF, PDGF and KIT recep-
tors in patients with platinum-resistant GCT. A
significantly higher progression-free survival (PFS)
rate was seen in a murine testicular cancer xenograft
model when an angiostatic agent was combined
with carboplatin or cisplatin as compared with
either carboplatin–cisplatin or the angiostatic
agent alone.
PROGNOSTIC FACTORS
Given the fact that MOGCT are a rare subtype of
tumours, the identification of prognostic and predic-
tive factors has challenged researchers and clinicians
worldwide. The definitive study on prognostic factors
for MOGCT is still to be published, but recent efforts
clearly support the evidence that factors such as
stage at presentation, residual disease after primary
surgery, elevation of serum markers and maybe also
age at presentation could be strong prognostic
markers [12–14]. Murugaesu et al. [12], in a retro-
spective review of 113 patients, found in univariate
and multivariate analysis that initial International
Federation of Gynecology and Obstetrics (FIGO)
stage III or IV at diagnosis and simultaneous elevation
of serum markers AFP and HCG were significant
predictors of overall survival but could not correlate
age at diagnosis with prognosis. In agreement exclud-
ing age as a prognostic factor was the retrospective
review of Lai et al. [15] in 93 patients. They report that
initial FIGO stage III or IV and histology (immature
teratoma/ nondysgerminoma) was strongly associ-
ated with an increased risk of treatment failure. Also
of interest is the finding that the aforementioned
specific subhistological types (immature teratoma/
nondysgerminoma) and residual disease after
primary surgery were strongly associated with wor-
sening of the overall survival. In keeping with this
trend, Lee et al. [16] in a retrospective review of
57 patients from a single institution conclude that
the presence of residual disease after primary surgery
was the only risk factor for primary treatment failure
in multivariate analysis. This article exemplifies
the problem of trying to make sensible prognostic
conclusions in small numbers; there were only
10 patients with residual disease after chemotherapy.
It is debatable whether failure to resect residual dis-
ease should be considered a prognostic factor, as it is
really an endpoint. Obviously, only patients with
initially advanced disease can have residual disease
www.co-oncology.com 541
 Gynecologic cancer
following chemotherapy, and not surprisingly if that
disease is not resectable, these patients will do worse.
These studies do not identify age as a predictive or
prognostic factor, but age has indeed been identified
as a recurrence predictive factor in several studies
[14,17]. Lee et al. [17], from the South Korean Gynae-
cology Oncology Study Group, found in a retrospec-
tive study of 196 patients that age of 40 years or more
at presentation and FIGO stage of III or IV was
strongly associated with recurrence after primary
treatment. Supporting these results is the retrospec-
tive study of 123 patients with MOGCT by Mangili
et al. [14]. They confirm in their analysis that age
older than 45 years at presentation and, importantly,
treatment outside a referral centre was an independ-
ent predictor of recurrence. They also found that
FIGO stage greater than I and yolk sac histology were
independent poor prognosis indicators.
PRIMARY SURGERY AND SURGICAL
STAGING
Currently, primary fertility sparing surgery with a
complete surgical staging, including omentectomy,
peritoneal washings and peritoneal biopsies, is the
gold standard procedure for all stage I MOGCT
[1,13,18,19]. Classically, complete surgical staging
had to include retroperitoneal lymphadenectomy
with removal of bilateral pelvic and para-aortic
nodes [13], but recent studies [18–22] discussed later
in this review question the necessity of retroperito-
neal lymphadenectomy. Taking into consideration
the high sensitivity of MOGCT to cytotoxic chemo-
therapy, the role of major cytoreductive surgery is
questionable. These tumours have a potential dou-
bling time of just a few days, so if there are delays in
starting chemotherapy in patients whose tumour is
not completely resected, the remaining tumour can
rapidly regrow [1,13]. Only in the relatively small
number of patients who have completed their
family would a total abdominal hysterectomy with
bilateral salpingo-oophorectomy procedure be indi-
cated [1]. With regard to the necessity for retroper-
itoneal lymphadenectomy at surgical staging, it was
the study of Billmire et al. [21] in paediatric MOGCT
that concluded that MOGCTs have an excellent
survival despite advanced stage with the com-
bination of conservative surgical resection and
adjuvant cytotoxic platinum-based chemotherapy
regimes. More recently, Brown et al. [22] in a retro-
spective study of 262 patients, and Mahdi et al. [18]
with a cohort of 1083 patients, 493 of them having
had lymphadenectomy, support these findings on
the basis of the extreme rarity of lymph node
involvement in these tumours [22] and the fact that
the addition of lymphadenectomy did not result in a
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significant survival benefit in patients with disease
confined to the ovary. Reassuringly, there was no
evidence that either retroperitoneal lymphadenec-
tomy or even metastatic involvement in the retro-
peritoneal lymph nodes was an independent
predictor of survival in patients with MOGCT [18].
Surgical restaging of inadequately staged
patients
If a patient with presumed stage 1 disease is to be
offered surveillance but has not been adequately
staged, a good case could be made for a second
staging operation. Many experts favour monitoring
stage I patients in a close surveillance programme
with radiological imaging and serial monitoring of
tumour markers [1,13,19–24], as the prognosis of
early-stage MOGCT is excellent even if the patient
relapses during surveillance after primary surgery.
Adjuvant cytotoxic chemotherapy for this subgroup
of patients is not recommended [19,20], as chemo-
therapy has such a high chance of curing patients
who relapse during surveillance. Giving chemother-
apy to all stage 1 patients will result in the exposure
&
of most patients to unnecessary toxicity [25 ,26].
Second look surgery
There is no role for routine second look surgery in
patients who have a normal computed tomography
(CT) and/or MRI scan at completion of chemother-
apy. The Gershenson review of the second look
experience of the University of Texas in 1986 [27]
found that second look findings were negative in
almost all the patients (52 out of 53). If there is
residual disease after chemotherapy, serious con-
sideration should be made about resection. The
aim of this surgery is to remove any potentially
viable tumour or any deposits of differentiated ter-
atoma that could dedifferentiate in the future or
progressively enlarge, known as the growing tera-
toma syndrome. Patients with serially shrinking
masses of dysgerminoma can be watched, as these
are unlikely to contain viable cancer and can be very
difficult to resect [27]. If tumour markers remain
persistently elevated or rise after completing chemo-
therapy, a potentially resectable mass should be
sought. It should be remembered that some patients
might have a persistently elevated AFP that is related
to toxicity from chemotherapy and not the disease.
CHEMOTHERAPY USED AS ADJUVANT OR
FOR EARY STAGE DISEASE
The combination regimen of cisplatin, etoposide
and bleomycin (BEP) is the worldwide recognized
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Number 5
September 2013
 Management of germ cell ovarian tumours Vazquez and Rustin
standard treatment for both men and women with a
cure rate approaching 98% in early stages and 75%
in advanced stages [1,28]. This has been used ever
since Williams et al. [28] showed the superiority of
etoposide over vincristine, given its better efficacy
and better toxicity profile in the BEP regimen. Now
we know that many patients on surveillance do not
relapse, it is probable that many of the patients
given chemotherapy for early-stage disease in the
past were already cured before they started their
chemotherapy.
SURVEILLANCE STRATEGIES
There is increasing awareness of surveillance for
stage 1 ovarian GCTs. The importance of adequate
staging prior to offering surveillance was high-
lighted by an Italian study, which showed that all
three of those with stage 1 dysgerminoma who
relapsed out of 19 on surveillance had been inad-
equately staged [19]. The same group also investi-
gated 28 patients with stage I immature teratoma
[20]. Two out of nine relapsed after adjuvant chemo-
therapy whilst four out of 19 on surveillance
relapsed. Four of the relapses contained just mature
teratoma and were treated surgically, whereas two
who relapsed with immature teratoma also received
chemotherapy. The observation that all remained
free of recurrence at median follow-up of 59 months
confirms the safety of surveillance.
These articles confirm the views already
expressed by Patterson et al. [23] who questioned
the need of potentially toxic chemotherapy use in
a retrospective review of 37 patients with stage I
MOGCT treated with surgery only and followed up
subsequently in an intense surveillance programme.
They found that the relapse rates of these tumours
were 36% in the nondysgerminomatous group and
22% in the dysgerminomatous group. These relapsed
patients were subsequently treated with a platinum-
based regime and only one of these patients died from
chemoresistant disease, proving the conservative
approach to be safe and adequate. An earlier study
from the same group by Dark et al. [24] highlighted
the dangers of getting pregnant during surveillance,
as pregnancy makes it difficult to safely monitor
patients. A patient who became pregnant early dur-
ing surveillance in a nonspecialist centre presented
with very advanced disease and died from pulmonary
embolism while on chemotherapy. Many of these
studies include patients who were suboptimally
staged, so with better staging and improved imaging,
the percentage of true stage Ia patients is likely to fall,
and hopefully the relapse rate will also fall.
Although there is no doubt about the high effi-
cacy of adjuvant cytotoxic chemotherapy, general
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concern is recognized as cytotoxic chemotherapy
can expose patients to severe immediate and long-
&
term complications [25 ,26]. Matei et al. [26]
analysed in retrospect 132 patients with different
subtypes and stages of MOGCT who had been
previously treated with different chemotherapy
regimes (BEP, VAC, carboplatin- etoposide, cispla-
tin, vinblastine, bleomycin). The control group was
composed of healthy individuals. It was found that
although the general health status of chemotherapy
survivors was comparable to that of age-matched
controls, remarkably significant differences were
described; specifically, a higher incidence of hyper-
tension, hypercholesterolemia and neuropathy
was evident among the chemotherapy survivor sub-
group. Also, the recent review of long-term toxicity
after chemotherapy for testicular cancer by Haugnes
&
et al. [25 ] confirms that secondary malignant
neoplasms and cardiovascular disease represent
the most common potentially life-threatening late
effects, typically occurring more than 10 years
after treatment. However, other long-term effects,
including pulmonary toxicity, nephrotoxicity, neu-
rotoxicity, decreased fertility, hypogonadism and
psychosocial problems, can have a major impact
on quality of life.
The current trend is clearly towards close sur-
veillance for all patients with stage Ia disease, but at
present, there is no universally accepted surveillance
schedule. Ulahannan and Rustin [1] postulate a
surveillance schedule involving regular clinical
review with clinical examination, radiological imag-
ing including abdomen-pelvic intravaginal sono-
graphy at regular intervals and the monitoring of
tumour markers to detect relapse over a period of
10 years, with a gradual increase of the interval
between clinical appointments. This is summarized
in Table 2, which is also the current surveillance
schedule at Charing Cross and Mount Vernon Hos-
pitals. Of paramount importance is the patient
adherence to the demanding visit schedule, and
because the majority of the relapses occur in the
first 2 years, after initial diagnosis, it is of extreme
importance to advise patients against pregnancy
during these 2 years. Pregnancy will result in a
physiological increase of the serum levels of AFP
and HCG that will interfere with an adequate sur-
veillance of these markers. If as is likely in some parts
of the world that it is not possible to confidently
follow close surveillance, it is preferable to give
adjuvant chemotherapy than miss relapsing disease.
MANAGEMENT OF ADVANCED DISEASE
The cytotoxic platinum combination BEP continues
to be the gold standard for MOGCT [1]. Due to the
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 Gynecologic cancer

Table 2. Updated Surveillance Schedule for stage Ia ovarian germ cell tumours of the West London and Mount
Vernon germ cell supraregional networks
Time period Examination Pelvic U/S Tumour markers CXR

First year Monthly 2 Monthly Monthly 2 Monthly
Second year 2 Monthly 4 Monthly 2 Monthly 4 Monthly
Third year 3 Monthly 6 Monthly 3 Monthly 6 Monthly
Fourth year 4 Monthly ————— 4 Monthly 8 Monthly
Year 5–10 6 Monthly ————— 6 Monthly Annually

3–6 week after initial surgery: CT chest, abdomen and pelvis, if not performed preop. 3 months after initial surgery: Repeat CT or MRI, abdomen and pelvis, and
if normal, consider second look laparoscopy, if inadequate initial staging, or glial implants. 12 months after initial surgery: CT or MRI abdo and pelvis. Advised
not to get pregnant during first 2 years of surveillance. Clinical examination to include internal examination unless recent scan. Tumour marker follow-up:
Serum AFP and HCG, and CA 125 (regardless of initial value) weekly until normal range and then 2 weekly for 3 months. Pelvic U/S alternate visits (not when
CT or MRI scan) for 2 years if nonseminoma and 3 years if dysgerminoma in view of risk of contralateral tumours. CT, computed tomography; U/S, ultrasound.
Modified with permission from [1].

exquisite chemosensitivity of these tumour types,
these interventions should bring a cure rate
approaching 98%. The cytotoxic combination with
cisplatin, vincristine, methotrexate, bleomycin,
actinomycin D, cyclophosphamide and etoposide
(POMB/ACE) could be considered in those patients
thought to carry a worse prognosis, stage III or IV at
presentation or significantly raised levels of AFP or
HCG. Nevertheless, the rates of cure should be
around 90% in these cases [12].
MANAGEMENT OF REFRACTORY
DISEASE
At present, one of the major challenges that clinicians
and researchers face is the treatment of patients with
MOGCT who relapse after cytotoxic chemotherapy
with a platinum combination. The rarity of these
tumours leads to paucity of trials and studies limiting
the treatment options widely available for this sub-
group of patients. Nevertheless, valuable information
can be extrapolated from recent efforts towards the
treatment of refractory and platinum-resistant testic-
ular cancers. Einhorn et al. [29] reviewed 184 patients
with progressive disease after platinum-based cyto-
toxic chemotherapy subsequently treated with one
or two 3-day course of high-dose chemotherapy with
carboplatin and etoposide followed by infusions of
autologus peripheral blood haematopoietic stem
cells. Of these 184, 135 received this treatment as a
second-line therapy and 94 (70%) achieved a com-
plete response; 49 patients of these 184 patients
received this therapy as third line or later therapy
and 22 (45%) achieved a complete response proving
that GCTs can potentially be salvaged even in third-
line or later therapy. Further efforts should be encour-
aged to translate these results into the female cohort
of refractory MOGCTs.
&
Recently, Jain et al. [30 ] reported a phase II
study of 29 patients with refractory GCT treated
with at least two lines of cytotoxic treament with
the combination of oxaliplatin and bevacizumab
based on the effectiveness of this combination in
many solid tumours. Although the primary end-
point of 12 months disease-free survival was not
achieved, eight patients (27.6%) had objective
response including one complete remission with a
very reasonable associated toxicity. As previously
mentioned in this review, Oeschle et al. [11] report
the preclinical and clinical activity of Sunitinib in
patients with platinum-resistant GCT. A signifi-
cantly higher PFS rate was seen in a murine testicular
cancer xenograft model when an angiostatic agent
was combined with carboplatin or cisplatin than
with either carboplatin–cisplatin or the angiostatic
agent alone. Unfortunately, there are no series
showing more than an occasional patient with
relapsed ovarian GCT following chemotherapy
becoming a long-term survivor. Therefore, it is
essential that patients are treated optimally from
the outset.
CONCLUSION
MOGCT are rare tumours, usually in young women,
with an excellent prognosis. Fertility sparing surgery
with thorough staging should be considered for all
patients who desire to retain fertility. In view of the
high cure rate with chemotherapy, major cytore-
ductive surgery is usually limited to those patients
with residual disease after chemotherapy. Close sur-
veillance is increasingly being offered to patients
with adequately staged stage 1 disease, with the
majority thus avoiding the immediate and delayed
toxicity of chemotherapy. Three cycles of BEP
chemotherapy are the most commonly used regi-
men for patients with advanced disease. Those
patients who relapse following chemotherapy
remain a major challenge, as they have lower cure
rates than their male counterparts.

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 Management of germ cell ovarian tumours Vazquez and Rustin
Acknowledgements
None.
Conflicts of interest
There are no conflicts of interest.
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