08 - Radiol Clin N Am 2007 - Imaging of Uterine Cancer.pdf
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doi:10.1016/j.rcl.2006.10.009
167
RADIOLOGIC
CLINICS
OF NORTH AMERICA
Radiol Clin N Am 45 (2007) 167–182
Imaging of Uterine Cancer
Oguz Akin,
MD
a,b,
*, Svetlana Mironov,
MD
a,b
,
Neeta Pandit-Taskar,
MD
a,b
,LucyE.Hann,
MD
a,b
-
Endometrial cancer
-
Cervical cancer
-
Endometrial cancer
Screening and diagnosis
-
Tumor detection and staging
Ultrasonography
CT
MR imaging
-
The role of imaging in treatment planning
-
Posttreatment follow-up
-
Cervical cancer
Screening and diagnosis
Tumor detection and staging
-
The role of imaging in treatment planning
-
Posttreatment follow-up
-
Summary
-
Acknowledgments
-
References
Endometrial cancer
The American Cancer Society estimates that in
2006, 41,200 new cases of cancer of the uterine cor-
pus, mostly endometrial, will be diagnosed and
7350 women will die from this disease in the
United States
[1]
.
Endometrial cancer may develop from endome-
trial hyperplasia caused by unopposed estrogen
stimulation; it also may develop spontaneously.
Risk factors for developing endometrial cancer
include conditions leading to increased estrogen
exposure, such as estrogen replacement therapy
(without progestin), obesity, tamoxifen use, early
menarche, late menopause, nulliparity, and history
of polycystic ovary disease. Pregnancy and use of
oral contraceptives reduce the risk of endometrial
cancer.
Up to 90% of endometrial cancers are adenocar-
cinomas. Depending on the glandular pattern, they
are classified as well-differentiated (grade 1) to an-
aplastic (grade 3) tumors. Prognostic factors
include tumor grade and stage, depth of myome-
trial invasion, and lymph node status.
Most endometrial cancers are detected at an early
stage because of clinical assessment for postmeno-
pausal bleeding. Treatment options include surgery,
radiation, hormones, and chemotherapy, depend-
ing on the stage of the disease.
The 1-year relative survival rate for uterine corpus
cancer is 94%. The 5-year survival rate is 96% for
local disease, but it decreases to 66% for disease
with regional spread and 25% for disease with
distant spread.
Cervical cancer
The American Cancer Society estimates that in
2006, 9716 new cases of invasive cervical cancer
will be diagnosed and 3700 women will die from
this disease in the United States
[1]
. As Papanico-
laou (Pap) smearing has become more common,
incidence rates of cervical cancer have decreased
and preinvasive lesions of the cervix are far more
a
Weill Medical College of Cornell University, New York, NY, USA
b
Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY
10021, USA
* Corresponding author. Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York
Avenue, New York, NY 10021.
E-mail address:
akino@mskcc.org
(O. Akin).
0033-8389/07/$ – see front matter
ª
2006 Elsevier Inc. All rights reserved.
doi:10.1016/j.rcl.2006.10.009
radiologic.theclinics.com
168
Akin et al
commonly diagnosed than invasive cervical cancer.
Mortality rates also have declined as a result of pre-
vention and early detection.
Risk factors for developing cervical cancer
include infection with certain types of human pap-
illomavirus, early age at first sexual intercourse,
multiple sexual partners, multiparity, history of sex-
ually transmitted diseases, and low socioeconomic
status.
Cervical intraepithelial neoplasia (CIN) is con-
sidered a precursor lesion of cervical cancer. CIN
is characterized in three groups depending on cellu-
lar dysplasia: CIN 1, minor dysplasia; CIN 2, mod-
erate dysplasia; and CIN 3, severe dysplasia or
carcinoma in situ. Up to 40% of CIN 3 lesions
could develop into invasive cervical cancer if left
untreated. Squamous cell carcinoma accounts for
80% to 90% of cases of cervical cancer. Adenocarci-
nomas are rare but have a worse prognosis.
Preinvasive lesions (ie, lesions that have not yet
transgressed the basement membrane) can be
treated with electrocoagulation, cryotherapy, laser
ablation, or local surgery. Invasive cervical cancers
are treated with surgery, radiation, or chemotherapy
or a combination of these three methods.
Relative 1-year and 5-year survival rates for cervi-
cal cancer patients are 88% and 73%, respectively.
The 5-year survival rate is approximately 92% for
localized cervical cancer
[1]
.
Imaging has become an important adjunct to the
clinical assessment of uterine cancer. When inte-
grated with clinical findings, imaging findings can
optimize cancer care and aid in the development
of a treatment plan tailored to the individual pa-
tient. Traditionally, the pretreatment evaluation of
uterine cancer consisted of clinical evaluation,
laboratory tests, and conventional radiographic
studies. The conventional imaging studies for clini-
cal staging are being replaced by cross-sectional im-
aging studies, namely ultrasound (US), CT, MR
imaging, and positron emission tomography
(PET). This article focuses on the role of cross-
sectional imaging in the management of endome-
trial cancer and cervical cancer.
age 35 should be offered to women with or at risk
for hereditary nonpolyposis colon cancer
[1]
.
Definitive diagnosis of endometrial cancer is
made with endometrial sampling with endometrial
biopsy or dilatation and curettage. The tissue ob-
tained by endometrial sampling is examined under
a microscope and evaluated for cancerous or pre-
cancerous abnormalities.
Transvaginal US may be used in the initial evalu-
ation of women with postmenopausal bleeding
[3–5]
. US diagnosis is based on endometrial thick-
ness measurements in the anteroposterior dimen-
sion. The Society of Radiologists in Ultrasound
Consensus Panel recommends a cut-off value of
5mm
[3]
, but others have reported optimal results
using 4 mm as the upper limit for normal endome-
trial thickness
[6,7]
. With normal endometrial
thickness on transvaginal US, the risk of cancer is
in the range of 1% to 5.5%
[7,8]
. Transvaginal US
is reported to be useful for diagnosis of endometrial
abnormalities and carcinoma in women with ab-
normal bleeding even when endometrial biopsy
and hysteroscopy produce negative results
[9,10]
.
Abnormal uterine bleeding is an early symptom
of endometrial carcinoma, and there is no evidence
that screening asymptomatic women is of any ben-
efit, even in high-risk groups
[11,12]
. Women who
undergo tamoxifen treatment for breast carcinoma
have a 7.5% relative risk of endometrial cancer,
but routine screening is not recommended
[13]
.
Women with hereditary nonpolyposis colon cancer
have a 40% to 60% lifetime risk of endometrial can-
cer, but US surveillance in the absence of symptom-
atic bleeding does not offer any prognostic
advantage
[14]
.
Tumor detection and staging
Staging of endometrial cancer is based on surgico-
pathologic International Federation of Gynecology
and Obstetrics (FIGO) criteria. The TNM staging
system is based on the same criteria as the FIGO sys-
tem (
Table 1
)
[15,16]
. The FIGO staging system
uses findings from exploratory laparotomy, total
abdominal hysterectomy, bilateral salpingo-oopho-
rectomy, peritoneal washings, sampling, and
lymphadenectomy.
Surgical staging, however, is not suitable for
women who are not good surgical candidates
because of older age, obesity, and other medical
problems. Noninvasive cross-sectional imaging is
particularly helpful in such cases to depict the depth
of myometrial invasion, tumor extent, and presence
of lymphadenopathy. Pretreatment imaging im-
proves patient care by assisting in determining the
type and extent of surgery or radiation treatment.
Endometrial cancer
Screening and diagnosis
Endometrial cancer is most commonly seen in el-
derly women with dysfunctional uterine bleeding
[1]
. Approximately 12% of endometrial cancers oc-
cur in premenopausal women, however
[2]
. The
American Cancer Society recommends that all post-
menopausal women be informed about the risks
and symptoms of endometrial cancer and encour-
aged to report any bleeding or spotting. Annual
screening with endometrial biopsy beginning at
Imaging of Uterine Cancer
169
Table 1: TNM and International Federation of Gynecology and Obstetrics staging systems
for endometrial cancer
TNM
FIGO
T - Primary Tumor
TX
Primary tumor cannot be assessed
Tis
0
Carcinoma in situ
T1
I
Tumor confined to corpus uteri
T1a
IA
Tumor limited to endometrium
T1b
IB
Tumor invades less than one half of the myometrium
T1c
IC
Tumor invades one half or more of the myometrium
T2
II
Tumor invades cervix but does not extend beyond uterus
T2a
IIA
Endocervical glandular involvement only
T2b
IIB
Cervical stromal invasion
T3
III
Local and/or regional spread as specified in T3a, b, and/or N1
and FIGO IIIA, B, and C below
T3a
IIIA
Tumor involves serosa and/or adnexa (direct extension or
metastasis) and/or cancer cells in ascites or peritoneal
washings
T3b
IIIB
Vaginal involvement (direct extension or metastasis)
N1
IIIC
Metastasis to the pelvic and/or para-aortic lymph nodes
T4
IVA
Tumor invades bladder mucosa and/or bowel mucosa (bullous
edema is not sufficient to classify a tumor as T4)
N—Regional Lymph Nodes
NX
Regional nodes cannot be assessed
N0
No regional nodal metastasis
N1
Regional nodal metastasis
M—Distant Metastasis
MX
Distant metastasis cannot be assessed
M0
No distant metastasis
M1
IVB
Distant metastasis (includes metastasis to intra-abdominal
lymph nodes other than para-aortic, and/or inguinal lymph
nodes; excludes metastasis to vagina pelvic serosa, or adnexa)
Ultrasonography
Ultrasonography, especially with a transvaginal ap-
proach, is the initial imaging modality in patients
with suspected endometrial cancer. Endometrial
cancer most often appears as thickened endome-
trium that is more than 5 mm in a postmenopausal
woman or 15 mm in a premenopausal woman
(
Fig. 1
). Echogenicity varies, but alteration of endo-
metrial texture or focal increased echogenicity may
be seen
[17]
. These appearances are not specific and
can be observed in endometrial hyperplasia and
polyps
[18]
. Saline infusion sonohysterography
improves diagnosis for endometrial cancer with
reported 89% sensitivity, 46% specificity, 16% pos-
itive predictive value, and 97% negative predictive
value
[19,20]
. Risk of disseminating malignant cells
by saline infusion sonohysterography is small,
approximately 7%
[21]
.
Color Doppler US often reveals increased vascu-
larity with a multivessel pattern, in contrast to the
pedicle artery sign seen in endometrial polyps
[22–24]
. Spectral Doppler indices may have low-
impedance flow, but there is significant overlap in
Doppler indices of benign and malignant condi-
tions of the endometrium
[25]
.
Myometrial invasion is depicted as irregularity of
the endometrium-myometrium border and disrup-
tion of the subendometrial halo. The accuracy of US
for diagnosing the depth of invasion is approxi-
mately 73% to 93%, but US is better for grade 2-3
tumors and should not be used as the sole criterion
for the decision to perform extensive surgery
[26–28]
. Although US can be used to estimate
depth of invasion, a recent meta-analysis has shown
that contrast-enhanced MR imaging has better over-
all performance
[29]
.
CT
On CT, endometrial cancer remains relatively low
attenuation compared with myometrium after con-
trast administration (
Fig. 1
).
Early studies with conventional CT reported 84%
to 88% staging accuracy for endometrial cancer
[30,31]
. A more recent study with helical CT
reported a sensitivity of 83% and a specificity of
42% for the assessment of depth of myometrial
T0
No evidence of primary tumor
170
Akin et al
Fig. 1.
A 57-year-old woman with endometrial cancer. Transvaginal US (A), contrast-enhanced CT (B), and sagittal
T2-weighted (C) and postcontrast T1-weighted MR imaging (D) show a large endometrial mass (M). Note that
the low signal intensity junctional zone is intact (arrow)(C) and there is a smooth interface between the
mass and the myometrium (arrow)(D). These findings rule out myometrial invasion.
invasion and a sensitivity of 25% and a specificity of
70% for the depiction of cervical invasion
[32]
.CT
is limited for the evaluation of cervical extension
and depth of myometrial invasion. CT is most com-
monly used in the assessment of advanced disease.
CT can demonstrate invasion to the adjacent or-
gans, such as bladder and rectum. Distant metasta-
ses from endometrial cancer are most often seen in
the extrapelvic lymph nodes and peritoneum. CT is
a reliable method in the assessment of enlarged
lymph nodes. Peritoneal metastases on CT appear
as peritoneal thickening, soft-tissue masses, and as-
cites. Detection of small lymph node metastases
and peritoneal implants is difficult not only with
CT but also with other imaging methods, however.
presence of myometrial invasion is suspected if
there is an irregular endometrium-myometrium in-
terface. Dynamic postcontrast images are especially
valuable in demonstrating myometrial invasion
because endometrial cancer enhances less than
myometrium (
Figs. 1 and 2
).
Determining the presence of myometrial inva-
sion is a critical factor because in patients with
deep myometrial invasion (invasion >50% thick-
ness of myometrium), there is a six- to sevenfold in-
creased prevalence of pelvic and lumboaortic
lymph node metastases compared with patients
with myometrial invasion that is absent or less
than 50%
[33]
. The preoperative determination of
myometrial invasion helps in planning the extent
of lymphadenectomy.
Conditions that may render MR imaging evalua-
tion of endometrial cancer difficult include the
presence of an indistinct junctional zone in a post-
menopausal woman, an irregular and thickened
junctional zone in adenomyosis, myometrial thin-
ning by a large tumor, and myometrial distortion
by a large leiomyoma.
In the early 1990s, the overall staging accuracy of
MR imaging was reported to be 83% to 92%
[34–36]
. A more recent study confirmed these early
reports and showed that MR imaging had 87%
MR imaging
MR imaging is the most accurate modality for the
pretreatment evaluation of endometrial cancer. En-
dometrial carcinoma is usually seen as a mass that
is hypo- to isointense on T1-weighted images and
hyperintense or heterogeneous on T2-weighted im-
ages compared with myometrium. On T2-weighted
images if the normal low signal intensity junctional
zone is intact, myometrial invasion can be
excluded. If the junctional zone is not well seen be-
cause of atrophy or distention caused by a mass, the
Imaging of Uterine Cancer
171
Fig. 2.
A 76-year-old woman with endometrial cancer. Transverse (A) and sagittal (B) T2-weighted MR imaging
show a large endometrial mass (M) that extends to the cervix (arrows). Note that the junctional zone is disrupted
and the mass extends to the uterine serosa (short arrow)(A).
sensitivity and 91% specificity in assessing myome-
trial infiltration, 80% sensitivity and 96% specificity
for cervical invasion, and 50% sensitivity and 95%
specificity for lymph node assessment. There was
significant agreement between MR imaging and
surgicopathologic findings in assessment of myo-
metrial invasion (P < 0.001)
[37]
. Like all other
cross-sectional imaging methods, MR imaging is
limited in the assessment of lymph node status
because it does not allow clear differentiation be-
tween metastatic and nonmetastatic lymph nodes
of similar size.
A study using meta-analysis and bayesian analy-
sis showed that findings from contrast-enhanced
MR imaging significantly affected the posttest prob-
ability of deep myometrial invasion in patients with
endometrial cancer. In this study, the mean
weighted pretest probabilities of deep myometrial
invasion in patients with tumor grades 1, 2, and 3
were 13%, 35%, and 54%, respectively. Posttest
probabilities of deep myometrial invasion for
grades 1, 2, and 3 increased to 60%, 84%, and
92%, respectively, with positive MR imaging find-
ings and decreased to 1%, 5%, and 10%, respec-
tively, with negative MR imaging findings
[38]
.
of myometrial invasion is important. Tumor exten-
sion into the cervix affects the type of surgery, and
parametrial invasion requires radiation as the ini-
tial treatment or a more radical surgical approach.
The value of US, CT, and MR imaging for diagno-
sis of myometrial invasion and cervical extension
has been assessed. Several reports have indicated
that MR imaging, being more accurate than CT
and US, is the most advantageous technique for
the evaluation of endometrial cancer
[40–42]
.A
meta-analysis showed no significant differences in
the overall performance of CT, US, and MR imag-
ing. For the assessment of myometrial invasion,
however, contrast-enhanced MR imaging per-
formed significantly better than did non-enhanced
MR imaging or US (P < 0.002) and demonstrated
a trend toward better results, as compared with
CT. The lack of data on the assessment of cervical
invasion at CT or US prevented meta-analytic com-
parison with data obtained at MR imaging
[43]
.
The following guidelines can be used for staging
endometrial cancer
[43]
:
1. No imaging is required for a patient with grade 1
tumor and a non-enlarged uterus at physical
examination because the pretest probability of
myometrial, cervical, or nodal involvement is
low. If results from the physical examination
are inconclusive or if there is concomitant pelvic
disease, US, CT, or MR imaging can be used for
the initial radiologic investigation.
2. Patients with high-grade papillary or clear cell
tumors should undergo CT or MR imaging be-
cause there is a high pretest probability of nodal
involvement.
3. Patients with possible cervical involvement at
physical examination or with positive or incon-
clusive results from endocervical curettage
should undergo MR imaging, because this is
The role of imaging in treatment planning
Morphologic prognostic factors, including depth of
myometrial invasion, cervical extension, and lymph
node metastasis, influence the prognosis and treat-
ment options in endometrial cancer
[39]
. Lympha-
denectomy and pre- or postoperative radiation
therapy are indicated in patients at high risk of ex-
trauterine disease or lymph node metastasis. Be-
cause the probability of extrauterine disease and
lymph node metastasis correlates with the depth
of myometrial invasion, preoperative knowledge
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