CARCINOMA OF THE ENDOMETRIUM Wen Di , M.D.,Ph.D 2003-10-27 Carcinoma of the Endometrium 1 • One of the commonest gynecological cancers,especially in white Americans, • it occurs most often in postmenopausal women(up to 80%of cases)with less than 5% diagnosed under 40 years of age. 2003-10-27 Carcinoma of the Endometrium 2 There is no effective screening programme,but occasionally cervical smears contain endometrial cancer cells or double thickness endometrial ultrasonic thickness of 4mm or more indicates a need for endometrial sampling. 2003-10-27 Carcinoma of the Endometrium 3 Risk Factors The actual cause of this cancer is unknown. Estrogen given estrogen alone as postmenopausal hormone replacement therapy Estrogen secreting tumors of the ovary are associated with an increased incidence of endometrial carcinoma. 2003-10-27 Carcinoma of the Endometrium 4 There can be no doubt that oestrogen can alter the behaviour of this tumour but there is still a question about oestrogen as a primary causal agent. Approximately 75%of cases of endometrial cancer occur in the postmenopausal period when estrogen values are low and progesterone is absent.Nulliparity and PCO syndrome(with defective progesterone synthesis)carry an increased risk. 2003-10-27 Carcinoma of the Endometrium 5 Only a proportion of obese,diabetic and hypertensive women develop endometrial cancer and similarly only a proportion of women with endometrial cancer are obese, diabetic or hypertensive.The question remains whether estrogen is a causal agent, or is acting in its normal capacity as a growth factor and is really to be regarded as a co-carcinogen. 2003-10-27 Carcinoma of the Endometrium 6 2003-10-27 Carcinoma of the Endometrium 7 Oral contraception,especially after long term use,reduces the incidence of both endometrial and ovarian carcinomas. 2003-10-27 Carcinoma of the Endometrium 8 The endometrial hyperplasia induced by Tamoxifen produces endometrial polyps.A report in the Lancet in 1999 suggested a four-fold increase in endometrial carcinoma.. 2003-10-27 Carcinoma of the Endometrium 9 Symptomatology The usual presenting symptom of endometrial carcinoma is postmenopausal bleeding which carries a 10% risk of associated malignancy in the absence of hormone replacement therapy. Curettage,or endometrial sampling is mandatory. Postmenopausal discharge from pyometra carries a 50% risk of associated malignancy. Pain may occur with pyometra or metastatic spread. 2003-10-27 Carcinoma of the Endometrium 10 Diagnosis Hysteroscopy with endometrial curettage or endometrial sampling,curettage alone, or outpatient endometrial sampling alone, are essential . Curettage is not infallible.On the other hand,if a Pipelle has been correctly introduced(record how many cm)and the pathology is benign, or no tissue is obtained,it is most unlikely that malignancy exists. 2003-10-27 Carcinoma of the Endometrium 11 Hysteroscopy,cervical smear(>1% risk of concurrent cervical malignancy) and vaginal or abdominal ultrasound for ovarian pathology are advised, when endometrial malignancy is found. 2003-10-27 Carcinoma of the Endometrium 12 2003-10-27 Carcinoma of the Endometrium 13 2003-10-27 Carcinoma of the Endometrium 14 2003-10-27 Carcinoma of the Endometrium 15 Further groups have been described. Adeno-squamoid group This has been divided into two groups: 1. If the squamous cells are well differentiated the tumour is termed adeno-acanthoma (Histological Grade 1) 2.Poorly differentiated squamous cells merit the name adeno-squamous carcinoma (Grade 2). 2003-10-27 Carcinoma of the Endometrium 16 2003-10-27 Carcinoma of the Endometrium 17 2003-10-27 Carcinoma of the Endometrium 18 Staging 2003-10-27 Carcinoma of the Endometrium 19 2003-10-27 Carcinoma of the Endometrium 20 2003-10-27 Carcinoma of the Endometrium 21 In general this cancer is slow to spread from the uterine cavity, probably because the endometrium lacks lymphatics. A chest X-ray helps detect lung metastases. Magnetic resonance imaging is preferable to ultrasound for detection of myometrial invasion and pelvic spread. 2003-10-27 Carcinoma of the Endometrium 22 Local Spread Slow invasion of the myometrium is the commonest spread. It may produce considerable uterine enlargement; or spread may involve the vaginal vault. 2003-10-27 Carcinoma of the Endometrium 23 Venous Spread This pathway might account for the occasional appearance of a low vaginal metastasis; but venous spread is not a common feature of uterine cancer. 2003-10-27 Carcinoma of the Endometrium 24 Lymphatic Spread The incidence of this (it is much debated) seems to be somewhere between 10 and 30%. All pelvic nodes, including the internal iliacs, the parametrium, the ovaries, and the vagina may be involved, probably with equal frequency. Lymphatic spread is more likely to occur when the tumour is anaplastic and the uterine wall is deeply invaded. 2003-10-27 Carcinoma of the Endometrium 25 Tubal Spread Malignant cells can pass along the tube in the same way that peritoneal spill may occur during menstruation. This may account for isolated ovarian metastases. 2003-10-27 Carcinoma of the Endometrium 26 2003-10-27 Carcinoma of the Endometrium 27 2003-10-27 Carcinoma of the Endometrium 28 PROGNOSIS OF ENDOMETRIAL CARCINOMA With the exception of stage 1 tumors of histological grades I and II, the prognosis is less favourable than many gyaecologists believe,with an overall 5 year survival of 70% approximately.Fortunately over 80 %of cases are dagnosed at stage 1. 2003-10-27 Carcinoma of the Endometrium 29 Staging diagnosis, extent of myometrial invasion and histological grading (differentiation)are the most important prognostic factors apart from competence of treatment. 2003-10-27 Carcinoma of the Endometrium 30 Stage I II III IV 2003-10-27 5 year survival 85% 68% 42% 22% Carcinoma of the Endometrium 31 Using both methods on similar cases we and that the 5-year survival rates for Stage I are the only ones altered significantly: Stage and histology 5-years survival I, G1 and 2 80% I,G3 60% 2003-10-27 Carcinoma of the Endometrium 32 TREATMENT OF ENDOMETRIAL CARCINOMA This is essentialy surgical,with postoperative radiotherapy added when unfavourable prognostic features are found at surgery.Pre-operative clinical Staging is inaccurate.Progestogen therapy is probab1y only of value in recurrent disease. 2003-10-27 Carcinoma of the Endometrium 33 Few women are unfit for surgery, and caesium insertion radioactive therapy may be employed for these,but radiation alone is less effective than combined surgical and radiation treatment. 2003-10-27 Carcinoma of the Endometrium 34 Stage I Total abdominal hysterectomy and bilateral salpingo-oophorectomy without partial removal of vagina. Peritoneal saline washings are taken for cytology on opening the abdomen and the Abdominal contents carefully examined.Vaginal hysterectomy with removal of ovaries, sometimes laparoscopy-assisted,has equal 5 year survival and lower operative mortality,in appropriate hands. 2003-10-27 Carcinoma of the Endometrium 35 Stage II Stage IIa carries a similar prognosis to Stage I and may be treated as stage I. Stage IIb,with clinical invasion of the cervix,has a poorer prognosis than Stage I and radical hysterectomy,pelvic lymphadenectomy and para-aortic lymph node sampling are indicated,with a combination of local and external radio therapy as an alternative treatment. 2003-10-27 Carcinoma of the Endometrium 36 Stage III Following the Staging laparotomy,radical hysterectomy,lymphadenectomy,paraaortic node sampling and removal of as much malignant tissue as possible, omentectorny is carried out.Stage III diseases limited to the pelvis may be treated by radiotherapy. 2003-10-27 Carcinoma of the Endometrium 37 Stage IV Treatment of this Stage is designed to control tumour growth and alleviate symptoms.Surgery, radiation therapy,cytotoxic therapy and adjuvant progestogen therapy all have a place. 2003-10-27 Carcinoma of the Endometrium 38 2003-10-27 Carcinoma of the Endometrium 39 The overall results are better than for carcinoma of the cervix,not because it is less malignant tumour, but because treatment is usually given earlier.Post-menopausal bleeding is much more difficult to ignore than the irregular bleeding of the younger woman. 2003-10-27 Carcinoma of the Endometrium 40 RECURRENCE OF ENDOMETRIAL CARCINOMA The incidence of recurrence within 5years is in the region of 30%and is accepted along with the 5-year survival rate as a measure of the effectiveness of the various systems of treatment.The majority recurrences appear within 3 years of treatment. Early recurrence has a poor Prognosis. 2003-10-27 Carcinoma of the Endometrium 41 PROGESTOGENS Many endometrial carcinomata are hormone dependent and progestogens have been used as part of a combined primary treatment as well as for recurrent or metastatic growths. 2003-10-27 Carcinoma of the Endometrium 42 Between 15%and 50%of recurrences will respond.Medroxyprogesterone acetate,400 mg to 600 mg daily,is most commonly employed and the addition of tamoxifen may improve the response. 2003-10-27 Carcinoma of the Endometrium 43 Chemotherapy Cytotoxic chemotherapy has a limited place in advanced recurrence.Single agent therapy with adriamycin, cisplatinum ,cyclophosphamide and hexamethylmelamine gives response rates between 20%and 40%. 2003-10-27 Carcinoma of the Endometrium 44 2003-10-27 Carcinoma of the Endometrium 45 Surgery gives poor results but chernotherapy,using vincristine, actinomycin D and cyclophosphamide has been reported as curative in 80% of children treated. 2003-10-27 Carcinoma of the Endometrium 46