ENDOMETRIAL CARCINOMA

Background

Most common gynaecological carcinoma in

developed countries

Japan and Asia have 5 times lower incidence

Most cases are post-menopausal

< 5% under age of 40 ( hyperestrogenic )

At diagnosis 75% have Stage 1 disease

OBESITY strong link as peripheral conversion to Estrone

SHBG(sex hormone binding globulin) decrease with an increase in FREE estrogen for uptake in target tissues

Lifetime risk: 1.1%

Lifetime risk of dying: 0.4%

5-year survival rates are considered to be

good at around 75%

The prognosis is generally good because the majority

of patients are diagnosed in an early stage

Role of hormones (estrogen)

Estrogen dependent disease

Prolonged exposure without the balancing effects of progesterone

Conditions of Estrogen excess

Early Menarche and Late Menopause

Associated with more estrogen exposure

Estrogen Replacement Therapy

Place women at high risk

Risk reduced when + progesterone

Tamoxifen

Anti-estrogenic drug for breast cancer

Side effect

Induces non-cancerous uterine tumors

Some may develop into endometrial cancer

Long term use => endometrial cancer

Only 1 in 500 develop endometrial cancer

Reduced Risk

Oral Contraceptives

Combined OC => 50% reduced rate

Actual reduction number small because uncommon in women of child bearing age

Long term offers protection

Reduced risk presumably => progesterone

Physical exercise and fruit vegetables diet

Endometrial Carcinoma: aetiology

Hyperoestrogenic states

Age - mainly 60-70 years (late menopause)

Parity - nulliparity, relative infertility

Metabolic disorders [Cancer Triad]

Obesity, Diabetes, Hypertension

Ovarian tumours

granulosa cell tumour, PCOD

unopposed Exogenous oestrogens [HRT]

other conditions

leiomyomas; adenomyosis, endometriosis, breast Ca

Risk factors

• Usually in postmenopausal women
• Unapposed estrogen stimulation
• Preceded by endometrial hyperplasia
• Simple hyperplasia

Adenomatous hyperplasia

Cellular Atypia

Clinical Features

Abnormal bleeding

mainly postmenopausal

intermenstrual or pre-menstrual

menorrhagia

Lower abdominal pain

abnormal vaginal discharge / pyometra

Endometrial Carcinoma

Diagnosis

Endometrial sampling

Dilation and curettage / Endometrial aspiration

Image

TVS / CT scan / MRI

Standard

Hysteroscopy + targeted biopsy

Tumor marker

Ca 125 / 199

Cystoscope / Proctoscope

Prevention

Early detection is best prevention

Treating precancerous hyperplasia

Hormones (progestin)

Hysterectomy

10 ~ 30% untreated develop into cancer

Histology/ grade

90% endometrial adenocarcinoma

Arise from the epithelium

Tumor grading

Grade 1

Well differentiated

Grade 2

Moderately differentiated with solid component

Grade 3

Poorly differentiated with solid sheets of tumor

Rare cell types

10% rare cell types

Papillary serous carcinoma

Clear cell carcinoma

Papillary endometrial carcinoma

Mucinous carcinoma

Rarer cancers

Onset at later age

Greater risk for metastases

Poorer prognosis

50% of treatment failure

Spread

Direct spread

Through endometrial cavity to the cervix

Through fallopian tubes to ovary / peritoneum

Invade myometrium reaching serosa

Rare: invasion to pubic bone

Lymphatic spread

Pelvic and para-aortic LN

Inguinal LN ( rare )

Hematogenous spread

Rare but may spread to lungs

Adenocarcinoma uterus

Intraoperatively obtained gross specimen of the uterus, bivalved in a sagittal plane, shows deep invasion (50% of the myometrial thickness) of endometrial carcinoma

Stage 1 Tumour confined to corpus

Stage 1a <50% myometrial invasion

Stage 1b >50% myometrial invasion

Stage 2 Tumour invades Cx stroma

Stage 3 Local/regional tumour spread

3a Invades serosa/+- adnexa

3b Vaginal or parametrial spread

3c1 Positive pelvic nodes

3c2 Positive para-aortic nodes

Stage 4 Invades bladder/bowel/distant

Treatment of endometrial hyperplasia/ carcinoma

Endometrial hyperplasia

Excessive stimulation of the uterine endometrium results in endometrial hyperplasia

Imbalance of hormones or hormonal changes can happen around the time of menopause, and contribute to the development of hyperplasia in some women.

Endometrial hyperplasia of the uterus, by itself, is not cancerous, but requires treatment and monitoring to prevent the risk of cancer.

Managing endometrial hyperplasia

Uterine hyperplasia can get worse, leading to atypical and precancerous cellular changes.

This is why any woman with hyperplasia is considered to be at a higher risk for cancer than one without hyperplasias.

investigate thickened endometrium,

hyperplasia can lead to uterine cancer —

early identification and intervention for uterine abnormalities is highly successful.

The evaluation process begins with a

speculum and bimanual exam

(internal exam and external palpation of the pelvic organs)

An ultrasound and tissue sampling

with endometrial biopsy, hysteroscopy and/or D&C

Hormonal treatment of endometrial hyperplasia

hyperplasia without atypia

progesterone/progestin therapy for three months,

then to retest the endometrium.

Provera

micronized natural progesterone at high doses

Atypia present

option for women who want to wait or avoid surgery altogether is Megace (megestrol acetate), a very potent, orally administered hormonal agent.

Ca Endometrium Treatment Algorithms

Clinical Stage I

TAH BSO

( Grade? Depth? Cell type ?)

Low Risk ~ 75%

Observation

High Risk ~ 25%

EBRT to pelvis

(but~13% have PA nodes)

Treatment of endometrial cancer

Stage II

Consider radical hysterectomy

With macroscopic tumor on cervix:

Consider a cervical cancer

Intra-abdominal spread:

Remove all tumor if possible

Advanced stage

Debulking surgery

Radiotherapy

+/- hormone / chemotherapy

Recurrence

Likely in women with advanced disease

Within 3 years of original diagnosis

Hormone therapy can be considered

External beam pelvic radiation or brachytherapy.