Epidemiology:

1/50 women in USA will develop EM cancer.

Age distribution: primarily in perimenopausal and postmenopausal women. Between 50 and 65. 5% under 40 y/o.
Risk factor:

Increase the risk:

Unopposed estrogen stimulation

Unopposed menopausal estrogen replacement therapy (4-8X )

Menopause after 52 y/o (24X)

Obesity ( 3X, 21-50 bl; 10X, over 50 bl).

Nulliparity (2-3X)

Diabetes (2.8X)

Feminizing ovarian tumor

Polycystic ovarian syndrome

Tamoxifen therapy for breast cancer ( more than two year)

* HER-2/neu oncogene overexpression in 10% EM cancer.

* P53 tumor suppressor gene overexpression

Diminishes the risk:

Ovulation

Progestin therapy

Combination oral contraceptives

Menopause prior to 49 y/o

Normal weight

Multiparity.

Symptoms, sign and diagnosis:

Symptom: Postmenopausal bleeding and abnormal perimenopausal bleeding.

Pap smear from exocervix can detect 50% of cases.

Dx: Fraction D&C, endometrial biopsy, hysteroscopy, vaginal ultrasound.

Histological types:

Adenocarcinoma: G1, G2, G3.

Adenoaquamous carcinoma: poor prognosis.

Clear cell adenocarcinoma: more worse prognosis.

Serous carcinoma: highly virulent, highly extrauterine spread.

Secretory carcinoma: good prognosis, 5-year survival rate: 87%.

Mucinous carcinoma: good prognosis

Squamous cell carcinoma: very poor prognosis.

Staging: ( see table & figure).

Prognostic factor:

Clinical factor:

Age at diagnosis: the younger, the better.

Race: white better than black.

Clinical tumor stage: ( see table).

Pathological factor:

Tumor grade: ( see figure)

Histological type: (see above)

Tumor size:

<= 2cm: 4% has lymph node metastasis.

>2cm: 15% has lymph node metastasis.

Entire EM cavity: 35% has lymph node metastasis.

Depth of myometrial invasion.

Microscopic involvement of vascular spaces in the uterus

Spread of tumor outside uterus to retroperitoneal lymph nodes, adnexa, peritoneal cavity.

Steroid receptor content. Stage I, II, III, IV - 65%, 50%, 17%, 0%.

Receptor positive has better prognosis.

* Ca-125 can be used to F/U if there were recurrent.

Pattern of spread of endometrial carcinoma: (See figure)

Management:

Stage I, Gr.I:

ATH + BSO.

If peritoneal cytology positive-15mCi of 32P intraperitoneally 2-3 wks post-op.

Stage I, Gr. II & III: ATH + BSO + pelvic lymph node sampling.

In stage Ic, R/T via vaginal implant with 5000 to 6000 rads or external pelvic R/T

Stage II: (1.) Radical hysterectomy + pelvic lymph nodes dissection

65 to 75% 5-year survival rate.

(2.) R/T + extrafascial hysterectomy. 70.6% 5-year survival rate.

(3.) R/T: 6000mg-hours of radium in uterus or 2500mg-hour of radium + 4000 rads external therapy. ?55% 5-year survival rate.

Stage III: Operative eradication with ATH + BSO and followed by postoperative external irradiation 40 to 50 Gy.

tage IV: Irradiation therapy.

Progestin ( 1000mg im Q1W) and /or combined with cytotoxic chemotherapy.

Chemotherapy:

Progestin: 10 to 20 % response rate.

Provera 1gm/week X 4wks as loading dose, then 400mg /week X 12wks.

Cytotoxic chemotherapy:

(Single dose)　　　　 (Response rate)
　　　　　Cisplatin　　　　　　　42%
　　　　cyclophosphamide　　 　　25%
　　　　5-fluorouracil　　　　 　　25%
　　　　Adriamycin　　　　　　　38%
　　(Combined chemotherapy)　 　50-60%
　　Ayoub et al.: Tamoxifen 20 mg QD x 3 wks then Provera 200mg QD
　　　　　+ Cyclophosphamide 400 mg/m2 D1&D8
　　　　　+ Adriamycin 30 mg/m2 D1
　　　　　+ 5-FU 400 mg/m2 D1&D8.
Hoffman et al.: Cyclophosphamide 250 to 500 mg/m2
　　　　　+ Adriamycin 30 mg/m2
　　　　　+ Platinum 50 mg/m2
　　　　　+ megestrol acetate 40 to 160 mg QD

Post-treatment ERT: (Creasman et al.)
Recurrence rate in non-ERT group: 14.7%; and in ERT group: 2.1%.

Overall 5-year survival rate: overall 72.7%
　Stage I: 86%
　Stage II: 66%
　Stage III: 44%
　Stage IV: 16%

Distant metastasis: most frequent site in lung(17%), retroperitoneal lymph nodes, upper portion of abdomen(10%), and bone(6%)