NM ENDOMETRIO: (Medical Radiology _ Radiation Oncology)

Endometrial cancer is the most common gynecologic malignancy and the 4th
most common cancer in women in the United States.
Risk factors of the disease include length of exposure of unopposed estrogen,
and the most common presenting symptom is postmenopausal bleeding.
Most (>90%) cases of endometrial cancer are adenocarcinoma.
Route of spread is through local extension, lymphatic or hematogenous. Stage,
depth of invasion, lymphovascular space involvement, and lymph node involvement
are the most important prognostic factors.
The majority of patients (>70%) are diagnosed early at stage I, leading to overall
good prognosis: >80% local control and >70% overall survival.
Surgery (total extrafascial hysterectomy with bilateral salpingo-oophorectomy,
peritoneal cytology, and pelvic/para-aortic lymph node dissection) is the mainstay
of diagnosis, pathologic staging, as well as treatment
Early-stage endometrial cancer can usually be treated with surgery with or
without radiation therapy.
Adjuvant radiation therapy (external-beam pelvic radiation and/or vaginal cuff
brachytherapy) has been shown to decrease local recurrence.
Locoregionally advanced endometrial cancer is treated with a combination of
surgery, radiation therapy, and chemotherapy.
Chemotherapy with or without hormonal therapy

Epidemiology and Etiology

There are 42,160 new diagnoses of endometrial cancer expected in the USA
in 2010. It is the 4th most common cancer in women, and ranks 8th among
causes of cancer death. It is the most common gynecologic malignancy.
Endometrial carcinoma arises from hyperplasia of the endometrial lining,
resulting from exposure to unopposed estrogens. Table 21.1 outlines the other
risk factors associated with this malignancy.
Anatomy
The uterus is a pelvic organ bordered by the bladder anteriorly and the rectum
posteriorly, and is covered by peritoneal reflections (Figure 21.1 and
Table 21.2).
Table 21.1 Risk factors of endometrial cancer
Risk factor Description
Patient related
Age: typical patients are postmenopausal between 55 and
85 years of age; incidence rate is higher than 95 per 100,000
women 6580 years of age
Endogenous estrogen exposure: early menarche, nulliparity,
infertility, late menopause, estrogen-producing ovarian
tumors
Exogenous estrogen exposure: hormonal replacement
therapy, hormonal replacement therapy, tamoxifen
Past medical history: hypertension, diabetes mellitus
Family history: although observed, < 1% of all endometrial
cancers are due to familial factors
Genetic predisposition: mutations in the MLH1 or MSH2
genes that mark the defect in HNPCC (Lynch syndrome II);
patients with this syndrome have a 20% risk of developing
endometrial cancer before age 50, and 60% before age 60
HNPCC: hereditary non-polyposis colon cancer
Anatomy Description
GrosAnatomic description of the uterus
Gross The uterus is divided into the fundus, isthmus, and the
cervix
The uterine wall has an outer smooth muscle layer (myometrium)
and an inner layer composed of glandular epithelium
(endometrium); the uterus is covered by a serosal
lining
Supported by 5 ligaments: broad, round, cardinal, uterosacral,
and vesico-uterine
Blood supply The uterine artery, a branch of the hypogastric artery, enters
the uterus at the isthmus
Lymphatics The myometrium drains into a rich subserosal lymphatic
network and joins larger lymphatic channels before exiting
the uterus
The fundus drains toward the adnexa and infundibulopelvic
ligaments; the middle and lower uterus drains in the
base of the broad ligament toward the pelvic sidewall
Nodal regions at risk: obturator, external iliac, internal
iliac, common iliac, and para-aortic

Diagnosis, Staging, and Prognosis

Clinical Presentation
The most common presenting symptom is vaginal bleeding. In postmenopausal
patients, vaginal bleeding is unexpected and may range from spotting
to heavy blood loss. Pre- or perimenopausal patients may present with menorrhagia
and/or metrorrhagia. Another presenting symptom is profuse, watery
discharge. Although uncommon, a routine Pap smear for cervical cancer
screening may detect abnormal endometrial cells.

Diagnosis
The diagnosis of endometrial cancer depends on the clinical presentation,
history and physical examination, including a thorough gynecologic examination,
imaging studies, and laboratory tests (Figure 21.2).
Tumor, Node, and Metastasis/Federation of Gynecology
and Obstetrics Staging
Endometrial cancer staging is determined by pathologic criteria. Recent
changes in the Federation of Gynecology and Obstetrics (FIGO) and the
American Joint Committee on Cancer (AJCC) staging recommendations
were made to coincide with prognosis and are reflected in Table 21.5.

No longer includes uterine sarcoma (now staged with a new staging system)
Positive peritoneal cytology is no longer considered (previously was T3a/
IIIA)
Involvement of the endocervical glands is not longer considered (previously
was stage IIA)
Stages IA and IB combined (now: IA). IC moved to IB
Stage IIIC subdivided into IIIC1 and IIIC2

Prognostic Factors
Survival is strongly influenced by the stage at diagnosis (Table 21.6). Adverse
prognostic factors include:
More advanced age: associated with higher chance of recurrence (age > 70
have more recurrence versus 5070)
 Higher grade: associated with higher chance of recurrence (grades 23)
Aggressive histology: clear cell adenocarcinoma, undifferentiated papillary
serous carcinoma are associated with worse prognosis due to more
distant failure pattern
Depth of myometrial invasion (>66%)
Lymphovascular space invasion
Gynecologic Oncology Group Trial 99 (GOG 99; Figure 21.4) outlines the
prognostic factors in directing treatment.

Principles and Practice

A total extrafascial hysterectomy with bilateral salpingo-oophorectomy, peritoneal
cytology, and pelvic/para-aortic lymph node dissection remains the
standard initial treatment for endometrial cancer. Traditionally done through
a vertical midline incision, a laparoscopic technique has recently been used.
Pathologic data has shown that certain high-risk pathologic features predict
higher rates of local recurrence. Therefore, adjuvant radiation therapy is recommended
for these patients. Systemic therapy is typically used in locoregionally
advanced, recurrent, or metastatic disease (Table 21.7).
Treatment of Early-Stage Endometrial Cancer
Surgical resection is the initial management of choice. The pathologic specimen
is then examined for the risk factors listed in Prognostic Factors along
with patient-related factors to determine a patients risk of locoregional recurrence.
The patient may be offered adjuvant therapy based on a significant
risk of recurrence (Table 21.8 and Figure 21.3).
EBRT: external-beam radiation therapy; 3D-CRT: 3-dimensional conformal radiation
therapy; IMRT: intensity-modulated radiation therapy; LDR: low-dose rate; HDR:
high-dose rate

Adjuvant External Radiation Therapy

Table 21.9 lists four randomized trials that evaluated adjuvant external-beam
radiotherapy versus observation after a surgical resection for early-stage endometrial
carcinoma. The general trend shows a local control benefit, but
this does not translate into a survival difference. Of note, there are inherent
differences between the studies with respect to lymph node surgical staging
and treatment with vaginal brachytherapy that make concrete conclusions
difficult to make.

As seen in the preceding tables and algorithm, there is a mixed recommendation

of treatment options for the intermediate risk group of patients. This
occurs due to the various disease- and patient-related factors that help make
a risk assessment. GOG 99 identifies this high-intermediate subgroup of patients,
and shows that adjuvant therapy may be more beneficial in this subgroup
(Figure 21.4).

Brachytherapy
Intravaginal brachytherapy may be given alone or in combination with external-
beam radiotherapy (EBRT), depending on the risk of pelvic lymph
node involvement. Alternatively, it may be omitted when external pelvic irradiation
is used as in the Post-Operative Radiation Therapy for Endometrial
Carcinoma (PORTEC) and GOG-99 studies, while maintaining good
locoregional control rates as shown in Table 21.9 (although the majority of
failures in these studies occurred at the vaginal cuff). The details of vaginal
brachytherapy technique and dose fractionation are discussed below.

Locoregionally Advanced Endometrial Cancer

Adjuvant Radiation Therapy
Patients with locoregionally advanced endometrial cancer as determined by
surgical pathology are recommended to undergo adjuvant pelvic irradiation.
Para-aortic irradiation may be added in cases where pelvic or para-aortic
lymph nodes are positive. Vaginal brachytherapy is often given in addition to
EBRT, due to the high risk of vaginal cuff recurrence.
Adjuvant Systemic Therapy
The GOG conducted a randomized trial to evaluate the role of adjuvant systemic
therapy, as seen in Table 21.10.

Radiation Therapy Techniques

Simulation and Field Arrangements
A computed tomography (CT) scan (2.50- to 5-mm cut) should be performed
from the top of L4 to the bottom of the lesser trochanters of the femurs. Aides
that may be used during the simulation included a Foley catheter, intravaginal
cuff marker, oral, and/or intravenous contrast. Organs at risk (see Table
21.17) should be delineated.
External radiation fields should encompass the vaginal cuff (or the entire
uterus in inoperable cases) and regional pelvic lymph nodes. Field setup is illustrated
in Figure 21.5 and Table 21.13.
Dose and Treatment Delivery
The pelvis is treated with external-beam radiation therapy to 4550 Gy in
2528 daily fractions using 6- to 18-MV photon beams.
and Intensity-Modulated Radiation Therapy,
and Target Volume Delineation
The benefits of three-dimensional conformal radiation therapy (3D-CRT)
and intensity-modulated radiation therapy (IMRT) radiation techniques are
to spare normal tissue while treating the target volumes (Figure 21.6 and
Table 21.14).
Definitions of gross tumor volume (GTV), clinical target volume (CTV),
planning target volume (PTV), and internal target volume (ITV) in 3D-CRT
and IMRT are as follows:
GTV: the entire uterus (in inoperable cases)
CTV: vaginal cuff, obturator lymph nodes, and external/internal/common
iliac lymph nodes
PTV: CTV plus 0.51.0 cm or ITV plus 0.5 cm
Organs at risk to be contoured are bladder, small bowel, rectum, bone marrow,
and the femoral heads.
Brachytherapy
Intravaginal brachytherapy allows the delivery of a high dose to the vagina
while minimizing dose to organs at risk. A vaginal cylinder is the most common
applicator used, and the largest diameter feasible is preferable. The radiation
is delivered with low-dose-rate (LDR) or high-dose-rate (HDR) radiotherapy.
The LDR prescription to the surface is 5060 Gy over 6070 h when
used alone. The prescription dose is reduced to 2530 Gy when combined
with EBRT. The HDR dose prescriptions as recommended by the American
Brachytherapy Society (ABS) are shown in Tables 21.15 and 21.16.