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Endometrial Cancer
Speaker : Shinenoam Chen
Department of OBS/GYN. VGHKS
Introduction
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Endometrial carcinoma is the most common
gynecologic malignancy in the United States.
Most cases are diagnosed at an early stage when
surgery alone may be adequate for cure.
Introduction
Type I endometrial carcinoma is estrogen-related:
1. tends to be associated with endometrial hyperplasia.
2. low grade endometrioid tumor
3. risk factors such as obesity, nulliparity,
endogenous or exogenous estrogen excess,
diabetes mellitus, and hypertension.
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Introduction
Type II endometrial carcinoma appears unrelated
to estrogen :
1. older , multiparous.
2. poor prognostic cell types, such as papillary
serous or clear cell tumors.
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ERT
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Estrogen Tx alone increases the risk for
endometrial hyperplasia and carcinoma.
Endometrial hyperplasia: 20-50% of women
receiving unopposed estrogen in one year.
RR: 3.1-15 (related to dose and duration)
ERT
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Risk can be reduced by the concomitant
administration of progestins.
Endogenous estrogen
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Functional ovarian tumors
Endogenous conversion of adrenal precursors into
estrogen by adipose cells (estrone hypothesis)
Higher circulating estrogen and androgen levels,
and lower SHBG levels.
Tamoxifen
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Competitive inhibitor of estrogen binding to
estrogen receptors.
adjuvant therapy in women with early stage breast
cancer, as treatment for recurrent disease, and for
reduction of breast cancer incidence in high-risk
women.
partial agonist activity, stimulating the endometrial
lining.
Tamoxifen
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2-3fold increased risk of endometrial cancer.
ACOG:the benefits outweigh the risks.
Recommendations :
1.Annually Gyn exam.
2.Report vagina bleeding
3.Tx limited to 5 years
4. Hysterectomy if atypical hyperplasia.
Obesity
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high levels of endogenous estrogen.
Conversion of androstenedione to estrone and the
aromatization of androgens to estradiol, both of
which occur in peripheral adipose tissue.
lower circulating levels of sex hormone binding
globulin.
Obesity
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Increased risk of death from endometrial cancer.
BMI ( 40 kg/m2) was 6.25-fold higher than that of
normal weight women.
Diabetes and hypertension
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Increased risk for endometrial cancer, associated
with obesity.
The effects of hyperinsulinemia, insulin resistance,
and insulin-like growth factors on endometrial
proliferation are under investigation.
Chronic anovulation(ex.PCOS)
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Adequate estrogen since androgens can be
converted peripherally to estrogens.
Lack the progesterone normally present in the
luteal phase.
constant estrogenic stimulation leading to
endometrial hyperplasia and endometrial cancer.
Age
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12 % of all patients with endometrial
adenocarcinoma were under 50 years of age.
Common features of these cases were obesity (56
percent had a BMI 30 kg/m(2)) and nulliparity
(44 percent).
Parity
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Nulliparity
High frequency of anovulatory cycles in infertile
(and thereby nulliparous) women.
Menarche and menopause
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Early menarche or late menopause was a risk
factor for endometrial cancer.
Prolonged estrogen stimulation without the
protection of progesterone is the presumed
mechanism.
Protective factors
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Oral contraceptives-progestin component suppresses
endometrial proliferation. The protective effect persisted
for at least 15 years after cessation of use.
Physical activity-changes in endogenous sexual and
metabolic hormone levels and growth factors, decreased
obesity and central adiposity, and changes in immune
function
Smoking-smoking stimulates hepatic metabolism of
estrogens.
HISTOPATHOLOGY
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The most common type of endometrial cancer is
endometrioid adenocarcinoma (75-80%).
Clear cell type(1-5%) and papillary serous
carcinomas(5-10%): much poorer prognosis
Well differentiated (gade I) : proliferation of
back-to-back endometrial glands without
intervening stroma. There is no more than 5%
solid growth.
HISTOPATHOLOGY
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Moderate differentiated (grade 2) tumors have
6-50% of the tumor composed of solid tumor
without glands, as well as greater nuclear atypia.
Poorly differentiated (grade 3) tumors contain
more than a 50% solid component.
CLINICAL PRESENTATION
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The classic symptom of endometrial
carcinoma is abnormal uterine bleeding.
20%of women with postmenopausal bleeding
will have endometrial cancer.
Pre- and perimenopausal women with
menometrorrhagia also should be evaluated.
Endometrial cells on Pap smear
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The presence of endometrial cells on a Pap smear
of a woman 40 years of age can signify
endometrial disease.
Endometrial disease was identified in 36%,
including endometrial hyperplasia in 13% and
adenocarcinoma in 11%.
Endometrial biopsy is recommended.
DIAGNOSIS
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Diagnosis of endometrial cancer is most easily
made by office endometrial biopsy.
Hysteroscopy with dilation and curettage (D&C)
remains the gold standard.
A higher grade based on the hysterectomy
specimen may be assigned in as many as 30% of
cases.
DIAGNOSIS
Transvaginal ultrasonography
• measuring the endometrial wall thickness
• In postmenopausal women, an endometrial
thickness of less than 4 to 5 mm is associated with
a low risk.
• The mean endometrial thickness in 759 women
with endometrial cancer is 20 mm.
DIAGNOSIS
Sonohysterography
• Differentiate Polyp or cancer.
• Biopsy or resection via the hysteroscope.
Pre-operative survey
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ECC
MRI- assess cervical involvement and depth of
myometrial invasion.
Tumor marker: CEA, Ca125, Ca199- predicting
extrauterine spread of endometrial cancer, and for
following patients after initial treatment
Deep invasion (>50% of the myometrial thickness) of
endometrial carcinoma (arrow).
TREATMENT
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Surgery
Chemotherapy
Radiation therapy
Hormone therapy
Surgery
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ATH+BSO+BPLND+ Paraaortic LN sampling.
Washing cytology.
MRH if cervix involved. (proved by ECC)
Laparoscopic lymphadenectomy combined with
vaginal hysterectomy, provide an acceptable
alternative to traditional laparotomy in patients
with early stage disease.
Endometrial cancer with <1/2 myometrial invasion
Surgical staging
*Grade 1.2
*No or minimal
myometrial
invasion
Observe
Ib or G3
Vagina radiaion
IbG3 or
Ic.II.III
Pelvic RT&vagina
Boost(extended
filed if positive
Para-aortic LN)
*Adnexal spread
*Intraperitoneal
dz completely
resected
Whole abdominal
radiation or C/T
Management of stage I and II endometrial cancer
Positive peritoneal
cytology
Observe or
progestins
Treatment by stage
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Stage Ib or G3 : vagina R/T
IbG3 or Ic: pelvic R/T.
Stage II: +C/T
Radiotherapy
Intermediate risk- Ic, II
adjuvant RT : vaginal cuff brachytherapy +/- external
beam RT is controversial.
*Reduction in the rate of vaginal or pelvic recurrence, but
not the survival.
• High riskvaginal cuff brachytherapy, pelvic external beam RT,
and whole abdominal irradiation (WAI).
*Reduce the likelihood of local recurrence, and possibly
prolong survival.
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Chemoherapy
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Regimens: PEI – Cisplatin + Epirubicin + Holoxan
( q3w X6 courses).
GOG122- Chemotherapy versus RT
-Stage III or IV
-WAI vs (doxorubicin 60 mg/m2 plus cisplatin 50
mg/m2 q3w for 7 courses, followed by an additional
course of cisplatin)
-Chemotherapy was superior to WAI in terms of two-year
overall survival.
Taxol+carboplatin
CCRT
Hormone therapy
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PR: PR(-) correlated to LN metastasis and poor
survival rate.
ER: less predictive than PR. Absence of ER was
predictive of recurrence for stage I tumors
Progestin (synthetic progesterone) may be used to
help stop the cancer from spreading.
response rate :30%
Decision tree concerning the treatment of recurrent endometrial
carcinoma.Legend: ENCA = endometrial carcinoma; QoL = Quality of Life;
RT = radiotherapy; HT = endocrine treatment; CHT = chemotherapy
Prognosis
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5 year survival:
S1G1
S1G2
S1G3
91%
84%
77%
S1
S2
S3
S4
90%
75%
60%
15%
Prognosis
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LN metastasis rate:
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Stage I: 10% ( stageII: 15%)
G1:3%
G2: 9%
G3:18%
<1/2M: 5%
>1/2M: 20%
Prognostic factor: Stage, grade, cell type, LN.