Endometrial Cancer

Balberan, Saro D. Canabal,Kelvin Vincent Flores, Marlo

Overview

Origin => Uterine endometrial lining Exact cause is unknown, increased levels of estrogen appear to play a role. Most common gynecologic malignancy 35,000 cases diagnosed each year Resulting in 4000 ~ 5000 deaths Normally occurs in postmenopausal Average age at diagnosis => 60 y/o < 5% under age of 40 Lifetime risk: 1.1% Lifetime risk of dying: 0.4%

Estrogen dependent disease

Prolonged exposure without the balancing effects of progesterone Endometrial hyperplasia Simple => 1% Complex => 3% Simple with atypia => 8% Complex with atypia => 29%

Premalignant potential

Incidence and Prevalence

Most common gynecologic cancer 4th most common in women (US) 2nd most common in women (UK) 5th most common in women (worldwide) Western developed > Southeast asia 35,000 new cases annually 5,000 death annually Increase in the 1970s

Increased use of menopausal estrogen therapy

Types

90% endometrial adenocarcinoma Arise from the epithelium Tumor grading

Grade 1

Well differentiated Moderately differentiated with solid component Poorly differentiated with solid sheets of tumor

Grade 2

Grade 3

10% rare cell types

Papillary serous carcinoma Clear cell carcinoma Papillary endometrial carcinoma Mucinous carcinoma Onset at later age Greater risk for metastases Poorer prognosis 50% of treatment failure

Rarer cancers

Risk Factors

Obesity

Excess weight have 2 ~ 5 x greater risk Fat cells (adipocytes) produce estrogen DM women have 2 x greater risk

Diabetes Mellitus and Hypertension

Irregular mentrual periods Infertility Nulliparity

Progesterone counterbalances estrogen Pregnancy lowers risk

Early Menarche (before age 12) and Late Menopause (after age 50)

Associated with more estrogen exposure Place women at high risk Risk reduced when + progesterone 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

Estrogen Replacement Therapy

Tamoxifen

Genetic Predisposition

Risk may approach 50% in some families

Previous Cancer

History of breast / colon / ovarian cancer are at increased risk Time interval can be as long as 10 years
Association is still unclear Diet rich in animal fat and protein => risk ^ Diet rich in vegetable, fruits, grain=> risk v

Diet

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

Tobacco Smoking

Some evidence that it reduces the rate Smokers have lower levels of estrogen and lower rate of obesity

Prevention and Survival

Early detection is best prevention Treating precancerous hyperplasia

Hormones (progestin) D&C Hysterectomy 10 ~ 30% untreated develop into cancer Stage I => 72 ~ 90% Stage II=> 56 ~ 60% Stage III => 32 ~ 40% Stage IV => 5 ~ 11%

Average 5 year survival

Signs

Postmenopausal vaginal bleeding Abnormal uterine bleeding

Bleeding in between periods Heavier / longer lasting menstrual bleeding

Abnormal vaginal discharge / Pyometra Pelvic or back pain Pain on urination Pain on sexual intercourse Presence of a lump Blood in stool or urine

Diagnosis

Endometrial sampling

Dilation and curettage / Endometrial aspiration

Image

TVS / CT scan / MRI

Hysteroscopy + targeted biopsy Ca 125 / 199

Standard

Tumor marker

Cystoscope / Proctoscope

Staging

Stage I

Tumor confined to uterine body Stage Ia

Tumor limited to endometrium Tumor invades less than of myometrium Tumor invades more than of myometrium

Stage Ib

Stage Ic

Stage II

Tumor extends to the cervix Stage IIa

Cervical extension limited to endocervical glands

Stage IIb

Tumor invades cervical stroma

Stage III

Regional tumor spread Stage IIIa

Tumor invades serosa / adnexa / peritoneum / ascites (+) Vaginal involvement / metastases present Tumor spread to pelvic LN

Stage IIIb

Stage IIIc

Stage IV

Bulky pelvic disease or distant spread Stage IVa

Tumor has spread to bladder or rectum

Distant metastases present / inguinal LN

Stage IVb

Spread

Direct spread

Through endometrial cavity to the cervix Through fallopian tubes to ovary / peritoneum Invade myometrium reaching serosa Rare: invasion to pubic bone Pelvic and para-aortic LN Inguinal LN ( rare ) Rare but may spread to lungs

Lymphatic spread

Hematogenous spread

Treatment

Surgery

Early stage ( I and II )

Typical surgery is ATH + BSO + BPLND VTH + BSO + laparoscopic BPLND LAVH + BPLND

Advanced stage
Debulking surgery Radiotherapy +/- hormone / chemotherapy

Radiation

External beam pelvic radiation

Reserve use of radiotherapy until post-ATH Adjuvant radiation therapy is controversial Regional pelvic radiation proven to decrease pelvic recurrence Not necessarily improve survival rate Most beneficial for patients with tumor confined to the pelvis Patients with increased likelihood of recurrence ( Stage Ic to IIIc)

Brachytherapy

Prevent vaginal cuff recurrence

Hormonal therapy

Progesterone => for metastatic cancer Less than 20% response rate No clear results on effectiveness Potentially most useful in metastatic cancer Not as important as surgery and radiation Only used in advanced or recurrent tumor after definitive treatment with surgery and radiation

Chemotherapy

Prognosis
Since it is possible to detect endometrial cancer early, the chances of curing it are excellent!
Survival Rates

5% 40% 90% Stage I Stage II Stage III Stage IV

60%

Prevention
Women report any abnormal vaginal bleeding or discharge to the doctor. All women should have regular pelvic exams beginning at the onset of sexual activity (or at the age of 21 if not sexually active) to help detect signs of infection or abnormal dev't. Controlling obesity, blood pressure, and diabetes help reduce risk. Using birth control helps prevent endometrium cancer. Taking medication that produces estrogen ask about receiving progesterone. If you are at risk, get screened regularly.

Thank you for your attention

Thank you for your attention