Original Research

ajog.org

OBSTETRICS

Mortality rate of gestational trophoblastic neoplasia

with a FIGO score of 13
Pierre-Adrien Bolze, MD; Ccilia Riedl, MD; Jrme Massardier, MD;
Jean-Pierre Lotz, MD, PhD; Benoit You, MD, PhD; Anne-Marie Schott, MD, PhD;
Touria Hajri, MSc; Franois Goler, MD, PhD

BACKGROUND: Gestational trophoblastic diseases include prema-

lignant (partial and complete hydatidiform moles) and malignant entities

referred to as gestational trophoblastic neoplasia. Use of the International Federation of Gynecology and Obstetrics prognostic score is
encouraged in cases of gestational trophoblastic neoplasia to predict the
potential for the development of resistance to single-agent chemotherapy. An International Federation of Gynecology and Obstetrics score
of
7 defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, treatment by specialized
centers, and reduction of early deaths at the time of chemotherapy
initiation have led to significant improvements in survival for patients with
high-risk gestational trophoblastic neoplasia. There is a crucial need for
the early identification of high-risk patients with gestational trophoblastic
neoplasia who have an increased death risk to organize their treatment in
highly specialized centers.
OBJECTIVES: The purpose of this study was to describe cases of
gestational trophoblastic neoplasia that have resulted in death, particularly
in a subgroup with an International Federation of Gynecology and
Obstetrics prognostic score of
13, for whom low-dose etoposide and
cisplatin induction chemotherapy recently was shown to reduce early
death rate.
STUDY DESIGN: We identified 974 patients from the French Center for
Trophoblastic Diseases who had a diagnosis of gestational trophoblastic
neoplasia from November 1999 to March 2014. Among 140 patients who
were at high risk of resistance to single-agent chemotherapy (International
Federation of Gynecology and Obstetrics score,
7), 29 patients (21%)

estational trophoblastic diseases

(GTD) include premalignant
(partial and complete hydatidiform
moles) and malignant entities that are
referred to as gestational trophoblastic
neoplasia (GTN), which encompass
invasive mole, gestational choriocarcinoma, placental site trophoblastic tumor
(PSTT), and epithelioid trophoblastic
tumor (ETT), the latter 2 being very

Cite this article as: Bolze P-A, Riedl C, Massardier J,

et al. Mortality rate of gestational trophoblastic neoplasia
with a FIGO score of
13. Am J Obstet Gynecol
2016;214:390.e1-8.
0002-9378/$36.00
2016 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2015.09.083

had a score of
13. Mortality rate was estimated with the use of the
Kaplan-Meier method.
RESULTS: The 5-year overall mortality rate, after the exclusion of
placental site trophoblastic tumors and epithelioid trophoblastic tumors,
was 2% for patients with gestational trophoblastic neoplasia (95% confidence interval, 1.25e3.13%). High-risk patients had a 5-year mortality
rate of 12% (95% confidence interval, 7.49e18.9%). Patients with
an International Federation of Gynecology and Obstetrics score of
13
had a higher 5-year mortality rate (38.4%; 95% confidence interval,
23.4e58.6%) and accounted for 52% of the deaths in the entire cohort.
Early deaths, defined as those that occur within 4 weeks after treatment
initiation, occurred in 8 patients of the entire cohort. Six of them had an
International Federation of Gynecology and Obstetrics score of
13 at
presentation, of whom 5 patients had brain and/or liver metastases.
CONCLUSION: Gestational trophoblastic diseases with an International Federation of Gynecology and Obstetrics score of
13 have an
increased risk of early death. We suggest that an International Federation
of Gynecology and Obstetrics score of
13 becomes a consensual criterion for prediction of patients with gestational trophoblastic neoplasia
with increased risk of death, particularly early death. These patients justify
treatment in highly specialized gestational trophoblastic disease centers
and may benefit from the use of induction low-dose etoposide and
cisplatin.
Key words: gestational trophoblastic neoplasia, FIGO score, high risk,

induction etoposide and cisplatin, mortality rate

rare entities.1,2 The French Center

for Trophoblastic Diseases has been
receiving voluntary declarations of GTD
cases since 1999; it provides pathologic
reviewing, supports clinicians for the
choice of treatment according to the
International Federation of Gynecology
and Obstetrics (FIGO) score, and organizes prospective follow-up evaluations.3
To date, >5000 patients with GTD have
been registered in the French Center for
Trophoblastic Diseases, of whom >1000
patients had GTN. Use of the FIGO
prognostic scoring system is encouraged
strongly in cases of GTN to predict the
potential for the development of resistance to single-agent chemotherapy.4
This prognostic score does not apply
to PSTT and ETT because single-agent

390.e1 American Journal of Obstetrics & Gynecology MARCH 2016

chemotherapy should not be the rst

therapeutic choice for these rare
tumors.2,5 A score of 6 denes a lowrisk of resistance, and patients should
be placed under methotrexate or dactinomycin.6 A score of
7 denes a high
risk and requires combination chemotherapy. The regimen that consists of
alternating EMA (etoposide, methotrexate, and dactinomycin) every week
with CO (cyclophosphamide and
vincristine) is the most widely used
regimen worldwide,7,8 even in the presence of other possible regimens, such as
bleomycin, etoposide, and cisplatin
(BEP) or dactinomycin, cisplatin, and
etoposide.6,7,9
Among the prognostic criteria that
inuence survival, the largest tumor mass

ajog.org

OBSTETRICS

diameter, the nature of the antecedent

pregnancy, and the sites of metastases
take part in the FIGO score.2 A high
FIGO score is associated with poor survival, where death is not only linked to
chemoresistance but also to early and
severe complications, such as hemorrhagic metastases, infection, multisystem
organ failure, or tumor lysis syndrome.10,11 Appropriate and rapid diagnosis, treatment by specialized centers,
and reduction of early deaths because of
chemotherapy initiation have led to signicant improvements in survival for
patients with high-risk GTN. A recent
study showed a 10-fold reduction in early
deaths with the use of induction low-dose
etoposide and cisplatin (EP) in 33 patients with high-risk GTN after exclusion
of nongestational diseases by genetic
analysis.8 In this study, induction
chemotherapy was given to patients with
a large disease burden, particularly within
the thorax, and to patients with brain
and/or liver metastases. These patients
had a higher number of metastases,
higher levels of serum human chorionic
gonadotropin (hCG), and/or higher total

FIGO scores. Therefore, a low-dose EPinduction protocol was implemented in

2012 in the French Center for Trophoblastic Diseases.
Here we present a retrospective analysis of the GTN cohort from the French
Center for Trophoblastic Diseases (from
1999-2014), focusing on death rates and
the inuence of FIGO scores of
13 as
a threshold for the identication of
patients who are at risk of early death.

Material and methods

This study was carried out at the French
Center for Trophoblastic Diseases in
Lyon. Informed consent for the prospective registration at the French Center
for Trophoblastic Diseases was obtained
from each patient, and ethical approval
was guaranteed from the local ethical
authority. Every registered patients
diagnosis was conrmed by our referent
pathologists.12 We identied 974 patients who had been diagnosed with a
GTN between November 1999 and
March 2014 from our electronic database. Patient characteristics are listed in
Tables 1 and 2.

Original Research

At the time of survival calculation, 4

patients were still under treatment at 15,
17, 20, and 25 months after treatment
initiation. The minimum follow-up
duration after data extraction in March
2014 was 1 year. The median follow-up
period of the entire cohort was 5 years
(range, 0-15 years); subgroup-specic
follow-up duration is reported in
Table 2. For 5 patients who had 2 distinct
cases of GTN, we analyzed only the latest
1. A FIGO score of
13 was chosen as a
cut-point because of its reproducibility
to identify patients with increased risk of
early death because of a large disease
burden. This criterion was present in
45% of patients who were treated by
induction low-dose EP by Alifrangis
et al.8 Among patients with a FIGO score
of
13, 16 patients who were identied
by the French Reference Center for
Trophoblastic Diseases were treated in
regional expert centers; 6 patients were
treated in specic anticancer centers, and
7 patients were treated in general hospitals, of whom 3 were treated outside
metropolitan France. First-line treatment of high-risk patients with a FIGO

TABLE 1

International Federation of Gynecology and Obstetrics score and stage of patients with gestational trophoblastic
neoplasia

International Federation
of Gynecology and
Obstetrics

Total number
of patients
(n 974), n (%)

International Federation of
Gynecology and Obstetrics
score, n (%)
6 (n 794)

7 (n 140)

Placental site trophoblastic

tumor-epithelioid trophoblastic
tumor (n 33), n (%)

Spontaneous
regression
(n 7), n (%)

19 (70.4)

stage
I

743

663 (83.6)

II

39

31 (3.9)

III

140

97 (12.2)

39 (27.9)

4 (14.9)

IV

43

2 (0.25)

39 (27.9)

2 (7.4)

Unknown

56 (40)
6 (4.3)

2 (7.4)

NA

3 (60)

score
0-4

685 (73)

682 (86)

5-6

113 (12)

112 (14)

NA

1 (20)

7-12

112 (12)

111 (79)

NA

1 (20)

13

29 (3)

29 (21)

NA

Unknown or not applicable

35

NA

NA, not applicable.

Bolze et al. Mortality rate of patients with GTN with a FIGO score of
13. Am J Obstet Gynecol 2016.

MARCH 2016 American Journal of Obstetrics & Gynecology

390.e2

Original Research

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OBSTETRICS

TABLE 2

Clinical characteristics of patients with gestational trophoblastic neoplasia

Clinical characteristic

Total patients
(n 941)

Median age, y (range)

33 (12e58)

Median human chorionic gonadotropin before treatment, IU/L

10,290

Rangea

4e4,022,380

Missing data, n

International Federation of Gynecology and Obstetrics

score
6 (n 794 )

7 (n 140)

13 (n 29 )

32 (12e57)

37 (18e58)

32 (18e50)

6,723

205,450

203,500

4e1,916,972

107e4,022,380

107e3,228,579

23

10

Antecedent pregnancy, n
Mole

787

731

53

Abortion

77

39

37

11

Birth

72

19

50

17

761

681

76

101

88

13

41

21

18

38

33

11

750

682

61

137

101

36

18

10

36

35

24

903

792

104

Unknown
International Federation of Gynecology and Obstetrics, n
Interval from antecedent pregnancy, y

Number of metastases score

Site of metastases score

27

27

20

15/902 (1.7)

0/765

15/133 (11.3)

10/29 (34.5)

Liver metastasis
n/N (%)

Not evaluated, n

36

29

Brain metastasis
n/N (%)
Not evaluated, n

17/833 (2.0)
104

Median follow-up period, y (range)

5 (0e15.1)

0/698
96
5.2 (0.6e15.1)

17/132 (12.9)

14/29 (48)

4.5 (0e15.1)

2.85 (0e12.8)

Total deaths, n

18

16

11

Early deaths, n

Note: Placental site trophoblastic tumors and epithelioid trophoblastic tumors were excluded.
a

Cases of human chorionic gonadotropin spontaneous normalization were excluded.

Bolze et al. Mortality rate of patients with GTN with a FIGO score of
13. Am J Obstet Gynecol 2016.

390.e3 American Journal of Obstetrics & Gynecology MARCH 2016

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OBSTETRICS

Results

FIGURE 1

Classification and 5-year outcome of patients with gestational trophoblastic

neoplasia from the French Center for Trophoblastic Diseases cohort

The treatment of GTN patients with PSTT or ETT was not decided according to FIGO score. Patients
with spontaneous remission of GTN without chemotherapy were excluded from analysis.
ETT, epithelioid trophoblastic tumor; FIGO, International Federation of Gynecology and Obstetrics; GTN, gestational trophoblastic
neoplasia; NA, not applicable; PSTT, placental site trophoblastic tumor.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of
13. Am J Obstet Gynecol 2016.

score of
13 consisted in EMA-CO (n

14), induction low-dose EP (n 6), BEP
(n 4) and dactinomycin, cisplatin, and
etoposide (n 4); 1 patient died before
treatment initiation. The total serum
hCG concentration was measured by
automated immunochemiluminescence
analyzers from the laboratory of each
patient center weekly until 1 month after
the end of treatment, then monthly
during 12 or 18 months for single-agent
or combination chemotherapy, respectively. Clinical and hCG follow-up evaluation was then eased. For PSTT and
ETT, hCG follow-up evaluation was
extended. After serum hCG normalization, consolidation consisted of 2 cycles
of chemotherapy. FIGO scoring and
staging was enabled by pelvic Doppler
ultrasound scanning, abdomen and
chest computed tomography (followed
by chest X-ray in case of lung metastasis), and brain and pelvic magnetic

Original Research

resonance imaging. The latest investigation was considered as reference for tumor size assessment. Any suspicion of
liver metastasis was further explored by
abdomen magnetic resonance imaging.
FIGO score and stage were extracted
from our database with PARADOX 9
software (Corel, Ottawa, Canada),
except for patients who were registered
before 2002, whose cases subsequently
were rescored (n 49). Early death was
dened as that which occurred within 4
weeks after treatment initiation. Survival
was calculated from the rst day of
treatment to 1 year after data extraction
or to the date of death. Survival was
estimated according to the FIGO score
with the use of the Kaplan-Meier
method, and a Wilcoxon test was used
to compare survival curves among
groups. Statistical analysis was performed with SAS software (version 9.2;
SAS Institute, Cary, NC).

Among 974 patients with GTN, 140 patients (14.4%) had a high-risk FIGO
score, of whom 29 patients had a score of

13 (Figure 1). The histopathologic
diagnosis was inconsistent with the
FIGO score for 33 patients (3.4%; 10
ETT and 23 PSTT) who were excluded
from high-risk patient analysis. Serum
hCG levels normalized in 7 patients
(0.7%; 4 with choriocarcinoma
conrmed by histology and 3 with a
clinical diagnosis of choriocarcinoma)
without the requirement for chemotherapy. The Kaplan-Meier estimate of
the 5-year overall death rate of the GTN
cohort (excluding PSTT and ETT) was
2% (95% condence interval [CI],
1.25e3.13%), which represented 18
deaths (2 low risk, 16 high risk). For
PSTT and ETT, the 5-year specic death
rate was 7.6% (95% CI, 1.9e28.1),
which represented 3 deaths. The median
time interval from treatment initiation
to death was 6.6 months (range,
0.1e64.4). The estimates of the 5-year
death rates for low- and high-risk patients were 0.3% (95% CI, 0.07e1.06)
and 12% (95% CI, 7.49e18.9), respectively. Among the high-risk patients, the
5-year death rate estimate was 38.4%
(95% CI, 23.4e58.6) and 4.9% (95% CI,
2.04e11.3) for cases that had a FIGO
score of
13 and <13, respectively
(p < .0001; Figure 2). High-risk patients
with a FIGO score of
13 accounted for
3% (29/974) of the entire GTN cohort.
Annual 5-year death rate varied from
0-4.5% for patients who were registered
until 2010 with no signicant trend.
However, the number of patients with
GTN who were registered in our center
increased from 25 in 1999 to 119 in 2010.
Among the entire cohort, 52% of
patients (11/21) who died had a FIGO
score of
13, and 6 of them died early.
Two other early deaths were identied
in the cohort, 1 death from massive
pulmonary embolism in a high-risk
patient (FIGO score, 8) and a second
death from intraperitoneal carcinomatosis from ETT origin (Figure 1). Three
quarters of early deaths (6/8) affected
high-risk patients with a FIGO score of

13; no early death happened in lowrisk patients.

MARCH 2016 American Journal of Obstetrics & Gynecology

390.e4

Original Research

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OBSTETRICS

Among high-risk patients with a FIGO

score of
13, death was caused by drugresistant GTN for 5 patients (46%) and
early complication that was linked with
treatment initiation for 6 patients: subarachnoid hemorrhage (n 3), multisystem organ failure (n 1), bilateral
pulmonary embolism (n 1), and septic
shock from cutaneous origin (n 1)
(Table 3). No signicant change was
noticed among the causes of death from
1999-2014. Antecedent pregnancy of
patients with a FIGO score of
13 was a
normal pregnancy in 17 of 29 cases
(59%), a spontaneous or legally induced
abortion in 11 of 29 cases (38%), and a
complete hydatidiform mole in 1 of 29
cases (3%). In 21 of 29 cases (72%), the
diagnosis of GTN was made after metastases were found. Initial imaging
revealed brain metastases in 14 patients
(48%), liver metastases in 10 patients
(34%), and lung metastases in every patient. Four patients (14%) had metastases in both liver and brain. Eight patients
(28%) had a FIGO stage III (GTN extends to the lungs with or without genital
tract involvement), and 21 patients
(72%) had a FIGO stage IV (all other
metastatic sites). Among 6 high-risk
patients with a FIGO score of
13 who
received induction low-dose EP (median, 2 cycles; range, 1e4 cycles), 3 patients died (50%; 1 was an early death.
Six high-risk patients with a FIGO
score of
13 died early, of whom 5 patients (83%) had brain and/or liver metastases (FIGO stage IV). Treatment by
EMA-CO, BEP, or induction low-dose
EP was initiated for 2, 2, and 1 of these
patients, respectively. One patient died
before any treatment could be initiated
(Table 3).

Comment
Data from the French GTN cohort
highlight that early initiation of suitable
treatment is associated with a 5-year
survival of 98%. This study corroborates the long-standing concept, recently
strengthened in a worldwide survey by
Kohorn,13 that centralized treatment of
patients with GTN is associated with the
lowest mortality rate.
The 5-year mortality rate (12%) of
high-risk patients with GTN (FIGO

FIGURE 2

Five-year overall survival of patients with gestational trophoblastic

neoplasia from the French cohort from 1999-2015

Patients were stratified according to the International Federation of Gynecology and Obstetrics
prognostic score at presentation.
ETT, epithelioid trophoblastic tumor; PSTT, placental site trophoblastic tumor.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of
13. Am J Obstet Gynecol 2016.

score,
7) is misleading because the

prognosis of these patients is denitely
different, with a 4.9% mortality rate in
cases with a FIGO score of <13 and
38.4% in cases with a FIGO score of
13.
This threshold of 13 seems to be highly
discriminatory for the death rate and
justies special attention for patients
with a FIGO score of
13.8 In this
subgroup, GTNs were derived from a
normal pregnancy approximately 60%
of the time, rather than from a hydatidiform mole, and were associated with
the presence of lung metastases in every
case, with brain and liver metastases in
one-half and one-third of the cases,
respectively.
One-half of the deaths in the high-risk
group with a FIGO score of
13 were
early deaths; only 1 early death occurred
in high-risk group with a FIGO score of
<13. Early deaths in patients with GTN
could be due to sudden and uncontrolled
hemorrhage of highly vascularized tumors and metastases.10,14 They can also
be associated with tumor lysis syndrome

390.e5 American Journal of Obstetrics & Gynecology MARCH 2016

that is related to chemotherapy initiation, because it frequently is described

in hematologic malignancies.15 Such a
tumor lysis syndrome was recently
described in GTN with the need of
rasburicase for treatment.11 Finally, early
death can result from severe sepsis as a
complication of chemotherapy.10 This
increased rate of early deaths among
patients with GTN with a FIGO score of

13 strongly indicates that such cases
would be best treated in highly specialized GTD centers with direct access to all
necessary major support services, which
include intensive care to cope with organ
system failures, interventional radiology
to deal with acute hemorrhagic problems, neurosurgery for raised intracranial pressure issues, and renal dialysis for
those patients with renal failure or in
whom renal failure is developing.
Early death prevention recently
was advocated as efcient with the
introduction of low-dose EP-induction
chemotherapy.8 This treatment, which
consists of etoposide 100 mg/m2 and

ajog.org

TABLE 3

Characteristics of dead high-risk patients with gestational trophoblastic neoplasia with an International Federation of Gynecology and Obstetrics score of 13
Human
chorionic
gonadotropin
level, IU/L

International
Federation of
Gynecology and
Obstetrics,
stage:score

First-line
chemotherapy

Time from
treatment
initiation
to death,
mo

Metastatic
disease
at diagnosis

Year of
treatment
initiation

Age,
y

Antecedent
pregnancy

2008

20

Birth

282,790

IV:18

BEP

0.6

Lung, mediastinum,
liver, bone, muscle,
skin, spinal dura

Drug-resistant disease

2009

20

Abortion

191,361

III:13

EA-CO

9.5

Lung

Drug-resistant disease

2010

28

Birth

42,449

IV:13

Death before
treatment

Lung, brain

Subarachnoid
hemorrhage

2010

18

Birth

205,450

IV:17

EMA-CO (high-dose
methotrexate)

0.1

Lung, spleen,
kidney, brain

Subarachnoid
hemorrhage

2010

34

Birth

319,813

IV:16

EMA-CO

0.6

Lung, liver

Bilateral pulmonary
embolism

2011

36

Birth

327,090

IV:15

BEP

0.2

Lung, vagina, bone,

muscle

Septic shock from

cutaneous origin

2011

26

Birth

867,450

IV:17

EMA-CO (high-dose
methotrexate)

29.9

Lung, liver, brain

Drug-resistant disease

2012

45

Abortion

661,284

IV:17

Low-dose etoposide
and cisplatin, then
EMA-CO (high dose
methotrexate)

5.5

Lung, brain

Multisystem organ
failure

2013

41

Birth

9,348

IV:17

EMA-CO

14.7

Lung, liver

Drug-resistant disease

10

2013

40

Abortion

120,957

III:13

Low-dose etoposide
and cisplatin, then
BEP

7.7

Lung

Drug-resistant disease

11

2014

28

Abortion

2,365,500

IV:15

Low-dose etoposide
and cisplatin

0.1

Lung, brain

Subarachnoid
hemorrhage

390.e6

Original Research

BEP, bleomycin, etoposide, and cisplatin; EMA-CO, etoposide, methotrexate, and dactinomycinecyclophosphamide and vincristine.
Bolze et al. Mortality rate of patients with GTN with a FIGO score of
13. Am J Obstet Gynecol 2016.

Cause of death

OBSTETRICS

MARCH 2016 American Journal of Obstetrics & Gynecology

Case
number

Original Research

OBSTETRICS

cisplatin 20 mg/m2 on days 1 and 2

that is repeated weekly for 1-2 cycles
before commencing EMA-CO, was
shown to decrease early death rate
from 11 of 140 (7.2%) to 1 of 140
(0.7%). In this series from Charing
Cross Center, low-dose EP induction
was used in patients who were
deemed to be at high risk of early
death, such as patients with extensive
disease in the chest, liver, or brain;
FIGO score of more than 12; and/or
major bleeding.8 The retrospective
analysis of this low-dose subgroup
pointed out that these patients
accounted for one-quarter of high-risk
patients with GTN (24%; 33/140) and
that their FIGO scores were higher
than the scores of patients who did not
receive low-dose EP. If a FIGO score of

13 had been the only inclusion criterion for low-dose EP-induction
chemotherapy in the French GTN
cohort, a similar proportion (21%; 29/
140) of high-risk patients would have
been treated according to this protocol.
The threshold of 13 for the FIGO
prognostic score is thus not only
discriminatory enough to identify patients with an increased death risk but
also to detect early death risk.
Because it is easily reproducible, we
suggest that a FIGO prognostic score
of
13 become a consensual criterion
for the prediction of patients with GTN
with increased risk of death, particularly
early death. These patients may benet
from the use of induction low-dose EP.
However, no data support the use of
induction low-dose EP in patients with
PSTT or ETT.
The major limitation of this study is
the voluntary declaration of cases to our
center. Although the nationwide
coverage has increased constantly since
its creation in 1999, not all GTN cases in
France are declared to our Center. As
such, there is the possibility of selection
bias. To minimize this risk, all patients
with GTN who were declared to the
French Center for Trophoblastic Diseases and followed prospectively were
included in this study. Because the
gestational origin was not conrmed
systematically by molecular genotyping,
we cannot exclude the presence of

nongestational trophoblastic tumors in

our study, which would increase the
mortality rate because of a poor prognosis of these non-gestational entities.
However, these are very rare tumors,
which represented only 6 of 396 patients
of the Charing Cross series.8 Finally, the
scarcity of patients with GTN with a
FIGO score of
13 may require our results to be supported by other centers
data in an international collaborative
work.
Despite a nearly 100% overall survival rate for GTN, high-risk patients
with a FIGO score of
13 are at
increased death risk, when compared
with patients with a FIGO score of <13.
They accounted for approximately 3%
of the French GTN cohort but included
more than one-half of its death cases
and almost all early deaths. Low-dose
EP induction was shown to decrease
early death rate. Therefore, we suggest
that a FIGO prognostic score of
13
become a consensual criterion for the
prediction of patients with GTN with
increased risk of death, particularly
early death. These patients may benet
from the use of induction low-dose EP
and justify treatment in highly specialized GTD centers with direct access to
all necessary major support services,
which include intensive care, interventional radiology, neurosurgery, and
renal dialysis. It is likely that this
appropriate treatment will be associated
signicantly with a decrease in overall
mortality rate in high-risk patients with
GTN.
n
Acknowledgments
The authors acknowledge the French Ligue
Nationale contre le Cancer and the Institut National du Cancer (INCa), which have recognized
the French Center for Trophoblastic Diseases as
a Rare Tumor Center since 2009 and which
renewed funding that enabled this study; the
French Center for Trophoblastic Diseases
thanks all the patients who, by giving their signed
consent, allowed for this study to be carried
out and all the physicians who declared
patients because such nationwide epidemiologic studies directly depend on their constructive collaboration.

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Author and article information

From the French Reference Center for Trophoblastic
Diseases, Lyon, France (all authors); the Department of
Gynecological Surgery and Oncology, Obstetrics, University of Lyon 1 (Drs Bolze, Massardier, and Golfier),
and the French Center for Trophoblastic Diseases (Drs
Bolze, Massardier, Hajri, and Golfier), University Hospital Lyon Sud, Pierre Benite, France; the Department
of Gynecology and Obstetrics, University of Limoges,

OBSTETRICS

University Hospital Me`re Enfant, Limoges, France (Dr

Riedl); the Department of Prenatal Diagnosis, University Hospital Femme Mere Enfant, Bron, France (Dr
Massardier); the Medical Oncology and Cellular Therapy Department, Hospital Tenon, Public Assistance
Hospitals of Paris, Alliance for Cancer Research
(APREC), Paris, France (Dr Lotz); Medical Oncology,
Investigational Center for Treatments in Oncology and
Hematology of Lyon, Centre Hospitalier Lyon-Sud,
Hospices Civils de Lyon, Pierre-Benite, France (Dr
You); Pole Information Medicale Evaluation Recherche,
Hospices Civils de Lyon (Drs Schott and Hajri), Lyon,
France.

Original Research

Received May 21, 2015; revised Aug. 26, 2015;

accepted Sept. 23, 2015.
Supported by a fellowship from the Nuovo-Soldati
Foundation for cancer research and from the Colle`ge
National des Gynecologues et Obstetriciens Francais
(CNGOF; P.A.B.); the French Center for Trophoblastic
Diseases was funded by the French Ligue Nationale
contre le Cancer and the Institut National Du Cancer
(INCa).
The authors report no conflict of interest.
Corresponding author: Francois Golfier, MD, PhD.
francois.golfier@chu-lyon.fr

MARCH 2016 American Journal of Obstetrics & Gynecology

390.e8