Endometrial Cancer

1. Endometrial Cancer Tseng Jen-Yu 02/05/2007

2. Overview • Origin => Uterine endometrial lining • 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%

3. Estrogen dependent disease • Prolonged exposure without the balancing effects of progesterone • Premalignant potential • Endometrial hyperplasia • Simple => 1% • Complex => 3% • Simple with atypia => 8% • Complex with atypia => 29%

4. 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 1970’s • Increased use of menopausal estrogen therapy

5. Types • 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

6. 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

7. Risk Factors • Obesity • Excess weight have 2 ~ 5 x greater risk • Fat cells (adipocytes) produce estrogen • Diabetes Mellitus and Hypertension • DM women have 2 x greater risk • Nulliparity • Progesterone counterbalances estrogen • Pregnancy lowers risk

8. 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

9. 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 • Diet • Association is still unclear • Diet rich in animal fat and protein => risk ^ • Diet rich in vegetable, fruits, grain=> risk v

10. 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

11. Prevention and Survival • Early detection is best prevention • Treating precancerous hyperplasia • Hormones (progestin) • D&C • Hysterectomy • 10 ~ 30% untreated develop into cancer • Average 5 year survival • Stage I => 72 ~ 90% • Stage II=> 56 ~ 60% • Stage III => 32 ~ 40% • Stage IV => 5 ~ 11%

12. 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 • Blood in stool or urine

13. Diagnosis • Endometrial sampling • Dilation and curettage / Endometrial aspiration • Image • TVS / CT scan / MRI • Standard • Hysteroscopy + targeted biopsy • Tumor marker • Ca 125 / 199 • Cystoscope / Proctoscope

14. Staging • Stage I • Tumor confined to uterine body • Stage Ia • Tumor limited to endometrium • Stage Ib • Tumor invades less than ½ of myometrium • Stage Ic • Tumor invades more than ½ of myometrium • Stage II • Tumor extends to the cervix • Stage IIa • Cervical extension limited to endocervical glands • Stage IIb • Tumor invades cervical stroma

16. Stage III • Regional tumor spread • Stage IIIa • Tumor invades serosa / adnexa / peritoneum / ascites (+) • Stage IIIb • Vaginal involvement / metastases present • Stage IIIc • Tumor spread to pelvic LN • Stage IV • Bulky pelvic disease or distant spread • Stage IVa • Tumor has spread to bladder or rectum • Stage IVb • Distant metastases present / inguinal LN

18. 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

19. 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

20. 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

21. Hormonal therapy • Progesterone => for metastatic cancer • Less than 20% response rate • Chemotherapy • 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

23. Recurrence • Likely in women with advanced disease • Within 3 years of original diagnosis • Hormone therapy can be considered • Use of chemotherapy is being evaluated • External beam pelvic radiation or brachytherapy

24. Thank you for your attention