Vol.2, No.7, 652-660 (2010)
doi:10.4236/health.2010.27099
Copyright © 2010 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Health
PET in uterine malignancies
Valeria Pirro1, Andrea Skanjeti1, Ettore Pelosi2*
1Nuclear Medicine Unit, San Giovanni Battista Hospital, University of Turin, Turin, Italy
2PET Centre, IRMET S.p.A., Turin, Italy; *Corresponding Author:
Received 7 March 2010; revised 2 April 2010; accepted 5 May 2010.
ABSTRACT
Positron Emission Tomography (PET) or inte-
grated PET/Computed Tomography (PET/CT)
with 18F-Flu o ro-D eoxy-Glucos e (18F-FDG) is a fu-
nctional imaging modality, useful in the char-
acterization of undetermined morphological fin-
dings, and in the staging/re-staging of a large
number of malignancies. Although its use in
uterine malignancies has been poorly investi-
gated, in recent years the employment of this
technique has constantly increased. In this re-
view, we evaluate the role of PET (/CT) with 18F-
FDG in uterine malignancies (cervical and en-
dometrial cancers as well as uterine sarcomas),
underlying its advantages and discussing its
limitations. Metabolic and anatomic information
given by PET/C T with 18F-FDG could be use ful in
the evaluation of local and distant disease in-
volvement at the staging, in the detection of
disease recurrence, and in the evaluation of the
response after chemotherapy and/or radio-the-
rapy.
Keywords: 18F-FDG PET/CT; Ute rine Maligna nci es;
Cervical Cancer; Endometrial Cancer;
Uterine Sarc omas
1. INTRODUCTION
Positron Emission Tomography (PET) or integrated
PET/Computed Tomography (PET/CT) with 18F-Fluoro-
Deoxy-Glucose (18F-FDG) study is a functional, non
invasive whole body examination, that allows to metab-
olically characterize undetermined morphological find-
ings, stage/re-stage disease, evaluate treatment response
and monitor the therapy in a large number of malignan-
cies (lymphomas, lung, breast, colon-rectal cancer, etc).
In the genital tract of women the use of PET is contro-
versial and it is limited by the urinary excretion of the
18F-FDG, that interfere with the evaluation of uterus and
vagina, and by the numerous false positive findings re-
lated to the presence of physiological tracer uptakes in
the bowel, ovaries, and in the uterus itself. However, the
clinical introduction of integrated PET/CT tomography,
allowing the co-registration and the superimposition of
anatomical and functional images and thus the exact
localization of all the 18F-FDG uptakes, improved PET
diagnostic accuracy [1].
The aim of the presen t review is to discuss the role of
18F-FDG-PET or PET/CT (PET/(CT)) exam in the uterine
cervical cancer, in the endometrial adenocarcinoma and
in the uterine sarcoma.
2. LITERATURE SEARCH
For this review, in the matter of the role of 18F-FDG-PET
(/CT) in the above mentioned gynaecological malignan-
cies, a MEDLINE search has been performed in order to
find relevant articles. For all the evaluated malignancies
we included only primary studies and meta-analysis
published in the English language in the last five years.
We did not include case reports, and abstracts. For uter-
ine cervical cancer we used as keywords: uterine cancer,
cervical cancer, and uterine cervix carcinoma; while for
endometrial cancer we used: uterine corpus carcinoma or
neoplasm, and endometrial cancer. Finally, in the case of
uterine sarcomas, we used as keywords uterine sarcoma,
uterine carcinosarcoma, and uterine leyomiosarcoma. In
all of the above mentioned cases, each keyword was
always associated with Positron Emission Tomography,
PET/CT, and 18F-FDG-PET/CT. Furthermore, to com-
plete the search we look for in the bibliography of the
founded studies and considered the most recent and in-
teresting works.
3. CERVICAL CANCER
Cervical cancer is the third most common neoplasm in
women. Recent data report an incidence rate of about
42,000 new cases/year in the United States and in the
European Union [2,3] and 150,000 deaths/year world-

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wide [4]. In the last decades, the introduction of the Pa-
panicolau screening test (Pap-test) has allowed an in-
crease in the detection rate of pre-invasive lesions; in the
same time the mortality due to the invasive cervical
cancer has not substantially decreased [5,6].
To stage cervical cancer the International Federation
of Gynaecologists and Obstetrics (FIGO) staging system
is currently used [7,8]. In patients with small localized
carcinomas (stage IA and IB1) radical hysterectomy or
radiotherapy alone are equally recommended [9]. For
large lesions and/or locally advanced cancers (stage IB2–
IVA), chemo-radiotherapy is the treatment of choice
[10,11]. Tumour size, parametrial tissue involvement,
pelvic and/or para-aortic lymph node spread and deep
invasion of nearby organs are the most important prog-
nostic parameters at the diagnosis [12]. Patients with
these unfavourable prognostic factors are at high risk of
developing disease recurrence with an estimated recur-
rence rate rangi ng bet ween 23% and 3 5% [1 3,14].
Even if the assessment of local and distant disease ex-
tension is a crucial point both in the pre- and post-treat-
ment phases, however a standardized protocol to stage/
re-stage these patients has not been established [15]. In
particular, no imaging modalities are routinely used in
this work up, which is based on physical examination,
Pap-test, serum markers assay and surgical evaluation.
Currently, the use of 18F-FDG-PET/CT in the manage-
ment of patients with cervical cancer has been investi-
gated in different settings.
3.1. Staging
The assessment of the primary lesion is actually based
on the clinical examination and on morphological imag-
ing modalities, in particular MRI. One of the crucial data
is the presence of uterine parametrial invasion. In this
field, despite the presence of co-registered CT images,
the diagnostic performance of 18F-FDG-PET/CT is worse
than MRI, due to the lack of a good spatial reso lution. In
the local staging of 32 primary tumour s, Park et al. high-
lighted a higher number of false negative results at PET
scan than at MRI (3 and 1 case, respectively) [9]. Proba-
bly, in stage IA or IB the amount of disease is under or at
the limit of the PET system resolution and its detection
can be elusive. Moreover, the interference of urinary
activity, that of physiological processes (such as hor-
mone-dependent changes in the ovaries and endome-
trium during the phases of menstrual cycle) and some
benign pathologies (such as corpus luteum cysts, endo-
metriosis, inflammations, menstruations, etc.) can inter-
fere with the optimal evaluation of the primary lesion,
leading to difficulties in exam interpretation [12,16].
Some of these PET limitations can be reduced with prac-
tical expedients: for example, the urinary interference
can be avoided by emptying the bladder just before the
start of the exam, or by the hydration and administration
of diuretics, or by the continuous bladder irrigation to
dilute and remove the radioactive urine. On the basis of
these limitations, it is clear that, despite the on-going
technical improvements, PET is still unsatisfactory in the
evaluation of the primary lesion and particularly in the
identification of the deep uterine tissue involvement.
On the other hand, an application of PET exam in
these cases is actually under debate, i.e. the prognostic
value of the primary lesion 18F-FDG uptake. The tumour
18F-FDG uptake, generally measured by the maximum
Standardized Uptake Value (SUVmax), seems to be
strictly related to the behaviour and to the aggressiveness
of the tumour itself as in other malignancies (head and
neck, lung and oesophageal cancers). In uterine cancer
different authors reported an independent correlation
between the cancer SUVmax and: the lymph node status,
the disease response to chemo/radio therapy, the fre-
quency of pelvic recurrence, the disease free and the
overall survival [12,17-20]. In a study on 240 patients,
Kidd et al. [21] confirmed the correlation between the
SUVmax at the staging and the presence of lymph node
metastases. Moreover, Lee and colleagues [22] observed
a good correlation between SUVmax and DFS in early
stages of cervical cancer. From these experiences, it
seems that SUVmax could be a useful prognostic tool in
this cancer too.
In the pre-treatment disease staging, the identification
of nodal (loco-regional and para-aortic) and distant me-
tastasis are crucial points, which present prognostic and
therapeutic significance. In fact, in locally advanced
cervical cancer the 5 year survival rate is 57%, 34% or
12%, in node negative cases, pelvic nodes metastasis or
para-aortic nodes metastasis, respectively [23]. In a re-
cent meta-analysis, the most accurate method to study
lymph node involvement resulted to be the sentinel node
biopsy; however, this is a (minimal) invasive procedure,
that often requires the administration of anaesthetic
drugs, and that could lead to some complications. Among
the imaging tests, the authors of this meta-analysis af-
firm that PET/CT presents better accuracy than contrast
enhancement (CE) CT and MRI and that it could be used
to guide laparoscopic staging procedures [24]. In fact,
the sensitivity of CECT and/or MRI in identifying nodal
metastasis is very low. A Gynaecological Oncology
Group (GOG) study reported a sensitivity of 34% in the
detection of para-aortic lymph nodes by CECT [25].
Furthermore, in patients with gynaecological cancer and
CECT negative for lymph node metastasis, PET/CT
showed sensitivity and specificity of 50% and 83.3%
respectively [25]. The good accuracy of PET and PET/CT
scans in detecting lymph nodes has been established by

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the meta-analysis of Havrilesky et al., that assessed a
pooled sensitivity and specificity rate of 84% and 95%
for para-aortic lymph nodes and 79% and 99% for pelvic
lymph nodes [26]. More recently, other authors con-
firmed these results for PET [27-32]. Furthermore, it was
evidenced an increase in the accuracy for combined
PET/CT [7,25,33-36]. Finally, Yen et al, indicate that an
SUVmax of para-aortic lymph nodes greater than 3.3 is a
strong negative prognostic facto r in patients with locally
advanced disease in respect to recurrence and survival
rate [36]. On the other hand as reported by several au-
thors, the limit of PET in this field, is represented by the
significant number of false negative lymph nodes. This
pitfall is related to the limited spatial resolution of the
tomograph [31,37-39]. Kitajima et al. [40] attempted to
improve the accuracy of the exam performing a PET/
CECT scan. They found a per patient based sensitivity,
specificity, positive predictive value, negative predictive
value and accuracy of 50%, 90.9%, 66.7%, 83.3% and
80%, respectively, and per lymph nodes based sensitiv ity
specificity, positive predictive value, negative predictive
value and accuracy of 51.1%, 99.8%, 85.2%, 98.9% and
98.7%, respectively. On the other hand, Kim et al. [23]
advise the use of fused MRI/PET to increase the detec-
tion of lymph node metastasis. In conclusion, due to the
low sensitivity, the use of PET/CT study to stage lymph
nodes should be taken into account only for patients
presenting importan t co-morbidities and/or co ntraindica-
tions to the surgical approach.
3.2. Radiotreatment Planning
Radiation treatment is indicated in a large part of these
patients. The accurate definition of the treatment plan-
ning is mandatory in order to adequately radiate the tu-
mour and to spare near critical organs. As in other ma-
lignancies, the target volume of radiation beam is cur-
rently based on morphological examinations (such as
CECT and MRI), that allow high spatial resolution im-
ages with accurate anatomical definition [41]. However,
this staging modality presents some limitations [42] and
the adjunct of the metabolic study significantly improve
the identification of the target volumes, allowing the
identification of the viable part of the tumour, and im-
proving the staging [43,44]. When PET is used, the
Planning Target Volume in modified in around 20% of
cases [45]. Recently Chao [46] showed the utility of
PET/CT in assisting RT treatment planning of patients
with potentially curable lymph node metastases. This
new information together with the new radiotherapy tools
(such as intensity-modulated radiation therapy) allow a
decrease in the dose to surrounding healthy tissues, as
well as an increase to the target [41,47-50].
3.3. Re-Staging
An early detection and an accurate staging of disease are
crucial elements in order to plan the therapeu tic strategy
and to improve prognosis [51]. In asymptomatic patients
previously treated for cervical cancer, the increase of
serum levels of markers such as CEA, Ca19.9 and Ca125
is one of the signs of disease recurrence. However, tu-
mour markers are non disease specific and do not give
indications about the site of relapse and the amount of
disease. In disease re-staging, conventional CECT and
MRI are the most frequently used imaging modalities,
even if some limitations should be taken into account:
first of all, they are generally limited to o ne body district
(pelvis and/or abdomen); secondly, they are often unable
to identify cancer relapse in body districts which present
post-surgical or post-radiotherapy scars (good sensitiv ity,
but low specificity levels); thirdly, they are inaccurate in
characterizing small lymph nodes and in detecting the
peritoneal disease [52]. Therefore, as described by van
der Weldt [53] the results of the above-mentioned exams
are often inconclusive and equivocal, thus justifying the
use of PET. In this study the 18F-FDG-PET/CT scan
showed a good sensitiv ity and specificity: 92% and 93%
respectively. Furthermore, as reported in Table 1, dif-
ferent authors in the recent years investigated the use-
fulness of PET(/CT) in the suspect of recurrence, and all
of them showed high sensitiv ity and specificity levels. In
fact, PET gives a metabolic characterization of the body
structures independent to their anatomy, also allowing
the investigation of critical regions in which anatomy
has been modified [54]. Given this and due to the possi-
bility of identifying distant metastasis, the therapeutic
strategies are changed in about 25% of patients after
PET exam [26,28].
Table 1. Sensitivity and specificity levels (in percentages) of
18F-FDG-PET(/CT) in the assessment of disease recurrence in
cervical cancer.
Authors, year RefNo. of patients Sensitivity (%) Specificity (%)
Sakurai, 2005 [26]25 91.5 57.1
Lin, 2006 [24] 260 77.3 96.3
Amit, 2006 [24] 28 60 94
Sironi, 2007 [22] 25 93 100
Chung, 2007 [12] 52 90.3 81
Husain, 2007 [25] 20 100 73
Kitajima, 2008 [17]30 93 93
van der Weldt [53]40 92 93

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As regards the follow-up, Brooks [4] demonstrated
that PET/CT presents a good accuracy in detecting re-
currences in both asymptomatic and symptomatic women.
In his study, it was interestingly sh owed that the survival
of women with asymptomatic recurrences was superior
to the symptomatic subjects.
As regards the prognosis, the modifications of the
18F-FDG-uptake during the course of the treatment re-
presents an important predictor of tumour response and
patient’s survival [55]. Nishiyama [19] evaluated the role
of PET in monitoring the neo-adjuvant therapy in pa-
tients with advanced stages of gynaecological cancers. In
his study, PET showed an accuracy of 85% in predicting
response to the treatment, when the SUVmax was de-
creased more than 65%. However, larger studies are
needed to better define the PET role in this context [56].
4. ENDOMETRIAL CANCER
Endometrial cancer is a common malignant disease, be-
ing the fourth cancer in post-menopausal women. In
Europe, about 1 out of 20 new cancers’ cases interests
the endometrium and in the United States the incidence
rate is about 40,000 new cases/year [57,58]. As in cervi-
cal cancer, the surgical-pathological FIGO staging sys-
tem is used to address patients to the more appropriate
treatment. Patients with FIGO stage IA and IB (in-
volvement of less than 50% of myometrium thickness)
can be treated with a tumour resection, while patients
with stage IC (involvement of more than 50% of myo-
metrium thickness) the para-aortic lymphnode dissection
and the use of adjuvant chemo-radiotherapy is one of the
proposed therapeutic strategy, due to the fact that this
stage has a greater inciden ce of nodal and distant metas-
tasis, with a worse prognosis [59]. Generally, patients
with the clinical suspect of deep myometrial invasion
undergo further examinations (CT or MRI), in order to
assess the extra uterine disease spread.
The role of 18F-FDG-PET/CT in the management of
this neoplasm is not well defined due to the lack of con-
sistent data in the literature, and due to this reason uter-
ine corpus cancer is not included among appropriate
applications in oncology [4 5] .
Few small studies assessed the validity of PET alone
in the evaluation of primary endometrial cancer, show-
ing good levels of sensitiv ity (rang e 83.3 -96.7 % [59-61]).
Torizuka et al. affirmed the feasibility of PET study in
the assessment of myometrial involvement, reporting a
better diagnostic accuracy than MRI (86.4% versus
77.3% respectively) [59]. In fact, in this study the SUV
of the tumour correlated significantly with the depth of
the tumour invasion. Furthermore, the authors used SUV
of the primary tumour, dichotomized to 12, in order to
predict the depth of the tumour invasion. They showed
that SUV < 12 correlated significantly with superficial
invasion, while SUV > 12 correlated with profound in-
vasion of the tumour. However, due to th e limited spatial
resolution of the PET study, a limited size of invasion
could be missed, leading to false negative PET results
[62]. Recently, two randomized trials showed that in
early stages of endometrial cancer the routine pelvic
lymphadenectomy improves the staging, furthermore
this surgical staging correlated with prognosis of the
patients. However, the advantage gained was only fur-
ther knowledge, since no survival benefits were ob-
served in these patients. On the contrary, women that
undergo surgical staging have increase the risks of com-
plications. Therefore, the goal of the non-invasive stag-
ing in these women would be to select those patients in
whom the surgical staging could improve prognosis not
only the staging [63-65]. In regard to PET/CT, Park et al.
showed in a population of 53 patients weak levels of
sensitivity and specificity in the staging of primary le-
sions (89.4 and 50.5%, respectively) and in the staging
of regional lymph nodes (69.2 and 90.3%, respectively).
On the other hand, high accuracy levels were reported in
the detection of distant metastasis. The authors con-
cluded that there are two main advantages of 18F-FDG-
PET/CT in the preoperative assessment of endometrial
cancer: the good negative predictive value in predicting
lymph node metastasis, that allows avoidance of surgical
staging in poor candidates for such procedure; the high
accuracy in detecting distant metastasis [66]. However,
again it must be reminded that in the above mentioned
study, the negative pr edictive value (NPV) was good but
not excellent (98.9% in the pelv ic evaluation, decrease in
87.5% for the para-aortic nodes). Furthermore the NPV
was further investigated by Signorelli [63]. It was indi-
cated that in high risk early stages the high NPV could
be useful to avoid systemic lymphaedenectomy. In such
cases a de-bulking surgery of the involved nodes could
be sufficient. With the decrease of lymph node dimen-
sion, a progressive significant reduction of sensitivity
has been observed by Kitajima et al.: 93.3% for lesions
greater than 10 mm, 66.7% for lesions between 5 and 9
mm, and 16.7% for lesions smaller than 4 mm [67] Fur-
thermore, Inubashiri [68] observed in recent work that
18F-FDG-PET/CT cannot change the medical manage-
ment of the patients if a MRI is previously performed.
As indicated by some authors, in endometrial cancer
the major contribution of 18F-FDG-PET/CT could be in
the early assessment of disease recurrence after therapy
[60,69]. The go od performance of 18F-FDG-PET/ CT has
been confirmed by Kitajima et al. in a recent paper in-
cluding 30 patients, that sho wed an overall patient-b ased
sensitivity, specificity and accuracy of 93% [70].

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In conclusion, in endometrial cancer, the most rele-
vant indications obtained by PET are: the possibility of
detecting disease recurrence in asymptomatic patients
presenting an increase of the Ca125 serum levels; the
ability in distinguishing fibrotic tissue from viable le-
sions after the treatment; the metabolic definition of the
radiotherapy treatment planning. Encouraging results are
also available in the assessment of lymph nodes and dis-
tant metastasis during the disease staging.
5. UTERINE SARCOMAS
Uterine sarcomas are rare neoplastic diseases which
represent about a 2-4% of all uterine malignancies [71].
The histology is heterogeneous, but the more represented
variety are the leiomyosarcoma, the carcinosarcoma and
the endometrial sarcoma. These malignancies present an
extremely poor prognosis and, despite their rarity, they
are responsible for a large number of deaths every year,
in women with uterine cancer. As with t he be ni g n u terine
leiomyoma, clinical features are represented by vaginal
bleeding and pain. Therefore, during the diagnostic
process, the differential diagnosis is crucial. Unfortu-
nately, in the maj ority of cases this is o btained only after
surgery at the histopathological examination, because
morphological imaging (US and MRI) is often in conclu-
sive.
Therapeutic options in these cancers actually include
the surgery (hysterectomy) when the cancer is localized,
and chemotherapy if the tumour is locally and/or dis-
tantly extended. During the follow-up about one half of
Stage I cases develop a recurrence [72]. In the manage-
ment of sarcomas (soft tissues and bone sarcoma), the
current literature evidences discordant data on the accu-
racy and the usefulness of 18F-FDG-PET scan due to the
small number and to the heterogeneity of the included
cases; however, PET seems to be capable of differenti-
ating between low and high grade sarcomas, and in the
evaluation of residual disease after therapy [73]. In the
case of uterine sarcomas, some authors suggest the use
of PET study to distinguish between leiomyomas and
leiomyosarcomas [74]. The identification of distant me-
tastases could be another reason for the execution of a
PET scan in the staging of these patients. However, a
recent study presented that only 9% of patients per-
formed an 18F-FDG-PET scan as part of perioperative
imaging. [75].
Despite the spare chemotherapy response the preco-
cious and accurate detection of disease recurrence is
crucial. However, an effective diagnostic strategy for an
early identification of relapse is missing, and specific
serological tumour markers are not available. Even if, at
this moment, there is not enough ev id ence to valid ate th e
use of this exam in the follow up of asymptomatic pa-
tients and in the evaluation of clinically suspected recur-
rences, in this scenario 18F-FDG-PET/CT could be use-
ful. In fact in a recent study Ho and colleagues [76]
showed that PET scan could change the management in
falsely inoperable patients or showing distant metastases.
On the other hand Park et al. [77] showed that the PET
scan has a good impact in the surveillance of patients
with uterine sarcomas. In fact, in this study, PET scan,
show a very good accur acy (94,4%) in women with sus-
pected recurrence and a good sensitivity (87,5%) in as-
ymptomatic women and contribute to change the treat-
ment in 1/3 of the population. The results of the few
small reports are encouraging in this way, but not com-
pletely in agreement [72,76,77].
Further, clinical studies are needed to define the role
of 18F-FDG-PET/CT in uterine sarcomas.
6. CONCLUSIONS
In this review, we evaluated the role of 18F-FDG-PET/
CT in uterine malignancies. This safe, non invasive, im-
aging modality gives useful metabolic and anatomic
information, and, as in the other field of oncology, it is
beginning to play an important role in the management
of these patients. Despite the relatively low number of
studies, its usefulness in the assessment of lymph-nodal
involvement at the staging, in the detection and staging
of disease recurrence, and in the evaluation of the re-
sponse after chemo- and radio-therapy has been proved.
In fact the use of PET/CT in uterine cancer seems to be
controversial. Despite numerous and rigorous study
demonstrated the utility, gynecologic oncologist are not
very enthusiastic of this exam. In fact, such as Kizer et
al. [78] demonstrated in a recent study, when 83% of
them routinely order CT scan, only 28% of them rou-
tinely order PET/CT scan. Some of them believe that
PET/CT does not provide useful prognostic information
whereas others causes could be the difficulty to obtain
third party payment from the private paying clients. It
seems that the better staging of metastatic lymph nodes
or distant metastases, the very good negative predictive
value in early stages, the correlation of before/after
treatment PET result with the overall survival, data al-
ready available, have little impact and do not convince
the gynecologic oncologist. However, these data are
good sources for the planning of other prospective stud-
ies that could have a greater impact.
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ABBREVIATIONS
PET: Positron Emission Tomography;
CT: Computed Tomography;
PET/CT: integrated PET/CT;
CECT: Contrast Enhancement Computed Tomography;
18F-FDG: 18F-Fluoro-Deoxy-Glucose;
Pap-test: Papanicolau screening test;
FIGO: Federation of Gynaecologists and Obstetrics;
MRI: Magnetic Resonance Imaging;
SUVmax: Standardized Uptake Value;
DFS: Disease Free Survival;
GOG: Gynaecological Oncology Group;
RT: Radiotherapy;
CEA: Carcinoembryonic Antigen;
CA 19.9: Carbohydrate Antigen 19.9;
CA 125: Carbohydrate Antigen 125;
NPV: Negative Predictive Value;
US: Ultrasonography